Camptothecin
Encyclopedia
Camptothecin is a cytotoxic quinoline
alkaloid
which inhibits
the DNA
enzyme
topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs
. It was isolated from the bark
and stem
of Camptotheca acuminata (Camptotheca, Happy tree), a tree
native to China
. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility
and (high) adverse drug reaction
. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecin and various derivatives to increase the benefits of the chemical, with good results. Two CPT analogues
have been approved and are used in cancer
chemotherapy
today, topotecan
and irinotecan
.
, that includes a pyrrolo
[3,4-β]-quinoline moiety (rings A, B and C), conjugated
pyridone moiety (ring D) and one chiral
center at position 20 within the alpha-
hydroxy
lactone
ring with (S) configuration
(the E-ring). Its planar structure is thought to be one of the most important factors in topoisomerase inhibition.
.
CPT binds both to the enzyme and DNA with hydrogen bonds. The most important part of the structure is the E-ring which interacts from three different positions with the enzyme. The hydroxyl group in position 20 forms hydrogen bond to the side chain on aspartic acid
number 533
(Asp533) in the enzyme. It’s critical that the configuration
of the chiral carbon
is (S) because (R) is inactive. The lactone is bonded with two hydrogen bonds to the amino groups on arginine
364 (Arg364).
The D-ring interacts with the +1 cytosine
on non-cleaved strand and stabilizes the topo I-DNA covalent complex by forming hydrogen bond. This hydrogen bond is between carbonyl
group in position 17 on the D-ring and amino group on the pyrimidine
ring of +1 cytosine. Toxicity of CPT is primarily a result of conversion of single-strand breaks into double-strand breaks during the S-phase when the replication fork collides with the cleavage complexes formed by DNA and CPT.
. The open ring form is inactive and it must therefore by closed to inhibit topo I. The closed form is favored in acidic condition, as it is in many cancer cells
microenvironment.
CPT is transported in to the cell by passive diffusion
. Cellular uptake is favored by lipophilicity, which enhances intracellular
accumulation.
Lipophilicity makes compounds
more stable because of improved lactone partitioning into red blood cells and consequently less hydrolysis of the lactone.
CPT has affinity for human serum albumin (HSA), especially the carboxylate form of CPT. Because of that, the equilibrium
between the lactone ring and the carboxylate form is driven toward the carboxylate. Reduced drug-HSA interactions could result in improved activity.
unit also enhances its abilities, as in homocamptothecin. Substitution at position 12 and 14 leads to inactive derivative.
(C2H5) or chloromethyl (CH2Cl). These groups are able to react with the DNA in the presence of topo I which leads to more tumor
activity. It has also been shown that increasing the length of the carbon chain (in position 7) leads to increased lipophilicity and consequently greater potency and stability in human plasma
.
Other 7-modified CPT analogues are silatecans and karenitecins. They are potent inihibitors on topo I and both have alkylsilyl groups in position 7 which make them lipophilic and more stable. Silatecans or 7-silylcampthothecins have shown reduced drug-HSA interactions which contributes to its blood stability and they can also cross the blood brain barrier. DB-67 is a 10-hydroxy derivative and is among the most active silatecans. BNP1350 which belongs to the series of karenitecins exhibits cytotoxic activity and ability to overcome drug resistance
. Still another route to make CPT’s lipophilic is to introduce lipophilic substituents, such as iminomethyl or oxyiminomethyl moieties. One of the most potent compounds is the oxyiminomethyl derivative ST1481 that has the advantage to overcome drug resistance caused by transport systems.
Basic nitrogen
in a carbon chain at position 7 makes the compound more hydrophilic and hence more water-soluble. For example is a derivate called CKD-602, which is a potent topo I inhibitor and successfully overcomes the poor water solubility and toxicity seen with CPT.
Considerably greater activity can be achieved by putting electron-withdrawing groups like amino, nitro
, bromo or chloro at position 9 and 10 and hydroxyl group at position 10 or 11. But these compounds are relatively insoluble in aqueous solutions, which causes difficulty in administrations. Methoxy
group at both position 10 and 11 simultaneously leads to inactivity.
or ethylenedioxy group connected between 10 and 11 form a 5 or 6 membered ring which leads to more water-soluble derivates and increased potency. Researches have shown that ethylenedioxy analogues are less potent than methylenedioxy. The reason is the unfavorable steric interactions of ethylenedioxy analogues with the enzyme.
Adding amino or chloro group at 9th position or chloromethyl group at 7th position to these 10, 11-methylenedioxy or ethylenedioxy analogues results in compounds with even greater cytotoxicity but weaker solubility in water. To yield 10, 11-methylenedioxy or ethylenedioxy analogues with good water solubility a good way is to introduce a water solubilising substituent at position 7. Lurtotecan meets those requirements; it’s a 10, 11-ethylenedioxy analogue with a 4-methylpiperazino-methylene at position 7 and has shown a great potency in clinical researches.
A ring can also be formed between position 7 and 9, like position 10 and 11. That gives new opportunities to make water-soluble derivatives [5]. These hexacyclic CPT become more active when electron-withdrawing groups are put in position 11 and methyl or amino groups at 10. Exatecan is an example of hexacyclic CPT that has a 6 membered ring over position 7 and 9, and is 10-methyl, 11-fluoro substituted [4]. It is water-soluble and more potent than topotecan.
is sufficient to stabilize the enzyme-complex.
Another possible modification is to insert a methylene between hydroxyl and lactone on the E-ring yielding a seven membered β-hydroxylactone group, so-called homocamptothecin (hCPT). The hCPT’s hydroxyl has less inductive effect
on the carboxyl group which makes the lactone very reactive. This enhances the interaction of the free hydroxyl group optimally with topo I and the covalent complex that forms in its presence are more stable. The E-ring of hCPT opens more slowly and the opening is irreversible
. hCPTs exhibit enhanced human plasma stability because of decreased protein
binding and more affinity for red blood cells than CPT.
CPT is linked to a cyclodextrin
-based polymer to form the investigational anti-cancer drug CRLX101.
Quinoline
Quinoline is a heterocyclic aromatic organic compound. It has the formula C9H7N and is a colourless hygroscopic liquid with a strong odour. Aged samples, if exposed to light, become yellow and later brown...
alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
which inhibits
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
the DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
topoisomerase I (topo I). It was discovered in 1966 by M. E. Wall and M. C. Wani in systematic screening of natural products for anticancer drugs
DRUGS
Destroy Rebuild Until God Shows are an American post-hardcore band formed in 2010. They released their debut self-titled album on February 22, 2011.- Formation :...
. It was isolated from the bark
Bark
Bark is the outermost layers of stems and roots of woody plants. Plants with bark include trees, woody vines and shrubs. Bark refers to all the tissues outside of the vascular cambium and is a nontechnical term. It overlays the wood and consists of the inner bark and the outer bark. The inner...
and stem
Plant stem
A stem is one of two main structural axes of a vascular plant. The stem is normally divided into nodes and internodes, the nodes hold buds which grow into one or more leaves, inflorescence , conifer cones, roots, other stems etc. The internodes distance one node from another...
of Camptotheca acuminata (Camptotheca, Happy tree), a tree
Tree
A tree is a perennial woody plant. It is most often defined as a woody plant that has many secondary branches supported clear of the ground on a single main stem or trunk with clear apical dominance. A minimum height specification at maturity is cited by some authors, varying from 3 m to...
native to China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
. CPT showed remarkable anticancer activity in preliminary clinical trials but also low solubility
Solubility
Solubility is the property of a solid, liquid, or gaseous chemical substance called solute to dissolve in a solid, liquid, or gaseous solvent to form a homogeneous solution of the solute in the solvent. The solubility of a substance fundamentally depends on the used solvent as well as on...
and (high) adverse drug reaction
Adverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
. Because of these disadvantages synthetic and medicinal chemists have developed numerous syntheses of Camptothecin and various derivatives to increase the benefits of the chemical, with good results. Two CPT analogues
Analog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
have been approved and are used in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
today, topotecan
Topotecan
Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble derivative of camptothecin...
and irinotecan
Irinotecan
Irinotecan is a drug used for the treatment of cancer.Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1. In chemical terms, it is a semisynthetic analogue of the natural alkaloid camptothecin....
.
Structures
CPT has a planar pentacyclic ring structureStructure
Structure is a fundamental, tangible or intangible notion referring to the recognition, observation, nature, and permanence of patterns and relationships of entities. This notion may itself be an object, such as a built structure, or an attribute, such as the structure of society...
, that includes a pyrrolo
Pyrrole
Pyrrole is a heterocyclic aromatic organic compound, a five-membered ring with the formula C4H4NH. It is a colourless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles, e.g., N-methylpyrrole, C4H4NCH3...
[3,4-β]-quinoline moiety (rings A, B and C), conjugated
Conjugated system
In chemistry, a conjugated system is a system of connected p-orbitals with delocalized electrons in compounds with alternating single and multiple bonds, which in general may lower the overall energy of the molecule and increase stability. Lone pairs, radicals or carbenium ions may be part of the...
pyridone moiety (ring D) and one chiral
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
center at position 20 within the alpha-
Alpha carbon
The alpha carbon in organic chemistry refers to the first carbon that attaches to a functional group . By extension, the second carbon is the beta carbon, and so on....
hydroxy
Hydroxyl
A hydroxyl is a chemical group containing an oxygen atom covalently bonded with a hydrogen atom. In inorganic chemistry, the hydroxyl group is known as the hydroxide ion, and scientists and reference works generally use these different terms though they refer to the same chemical structure in...
lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
ring with (S) configuration
Chirality (chemistry)
A chiral molecule is a type of molecule that lacks an internal plane of symmetry and thus has a non-superimposable mirror image. The feature that is most often the cause of chirality in molecules is the presence of an asymmetric carbon atom....
(the E-ring). Its planar structure is thought to be one of the most important factors in topoisomerase inhibition.
Binding
CPT binds to the topo I and DNA complex (the covalent complex) resulting in a ternary complex, and thereby stabilizing it. This prevents DNA re-ligation and therefore causes DNA damage which results in apoptosisApoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
CPT binds both to the enzyme and DNA with hydrogen bonds. The most important part of the structure is the E-ring which interacts from three different positions with the enzyme. The hydroxyl group in position 20 forms hydrogen bond to the side chain on aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
number 533
Peptide sequence
Peptide sequence or amino acid sequence is the order in which amino acid residues, connected by peptide bonds, lie in the chain in peptides and proteins. The sequence is generally reported from the N-terminal end containing free amino group to the C-terminal end containing free carboxyl group...
(Asp533) in the enzyme. It’s critical that the configuration
Configuration
The term configuration has several meanings.In computing it may refer to:* Computer configuration or system configuration* Configure is the output of Autotools and used to detect system configuration...
of the chiral carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
is (S) because (R) is inactive. The lactone is bonded with two hydrogen bonds to the amino groups on arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
364 (Arg364).
The D-ring interacts with the +1 cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...
on non-cleaved strand and stabilizes the topo I-DNA covalent complex by forming hydrogen bond. This hydrogen bond is between carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
group in position 17 on the D-ring and amino group on the pyrimidine
Pyrimidine
Pyrimidine is a heterocyclic aromatic organic compound similar to benzene and pyridine, containing two nitrogen atoms at positions 1 and 3 of the six-member ring...
ring of +1 cytosine. Toxicity of CPT is primarily a result of conversion of single-strand breaks into double-strand breaks during the S-phase when the replication fork collides with the cleavage complexes formed by DNA and CPT.
Physical and chemical properties
The lactone ring in CPT is highly susceptible to hydrolysisHydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...
. The open ring form is inactive and it must therefore by closed to inhibit topo I. The closed form is favored in acidic condition, as it is in many cancer cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
microenvironment.
CPT is transported in to the cell by passive diffusion
Passive transport
Passive transport means moving biochemicals and other atomic or molecular substances across membranes. Unlike active transport, this process does not involve chemical energy, because, unlike in an active transport, the transport across membrane is always coupled with the growth of entropy of the...
. Cellular uptake is favored by lipophilicity, which enhances intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
accumulation.
Lipophilicity makes compounds
Chemical compound
A chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
more stable because of improved lactone partitioning into red blood cells and consequently less hydrolysis of the lactone.
CPT has affinity for human serum albumin (HSA), especially the carboxylate form of CPT. Because of that, the equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
between the lactone ring and the carboxylate form is driven toward the carboxylate. Reduced drug-HSA interactions could result in improved activity.
SAR – Structure-activity relationship
Studies have shown that substitution at position 7, 9, 10 and 11 can have positive effect on CPT activity and physical properties, e.g. potency and metabolic stability. Enlargement of the lactone ring by one methyleneMethylene
Methylene is a chemical species in which a carbon atom is bonded to two hydrogen atoms. Three different possibilities present themselves:* the -CH2- substituent group: e.g., dichloromethane ....
unit also enhances its abilities, as in homocamptothecin. Substitution at position 12 and 14 leads to inactive derivative.
Alkyl substitution
Alkyl substitution at position 7 has shown increased cytotoxicity, such as ethylEthyl
Ethyl may refer to:* Ethyl group, a functional group in organic chemistry* Ethyl Corporation, a fuel additive company* Ethanol, also known as ethyl alcohol* Cold Ethyl, a rock band founded by Nicke Andersson...
(C2H5) or chloromethyl (CH2Cl). These groups are able to react with the DNA in the presence of topo I which leads to more tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
activity. It has also been shown that increasing the length of the carbon chain (in position 7) leads to increased lipophilicity and consequently greater potency and stability in human plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
.
Other 7-modified CPT analogues are silatecans and karenitecins. They are potent inihibitors on topo I and both have alkylsilyl groups in position 7 which make them lipophilic and more stable. Silatecans or 7-silylcampthothecins have shown reduced drug-HSA interactions which contributes to its blood stability and they can also cross the blood brain barrier. DB-67 is a 10-hydroxy derivative and is among the most active silatecans. BNP1350 which belongs to the series of karenitecins exhibits cytotoxic activity and ability to overcome drug resistance
Drug resistance
Drug resistance is the reduction in effectiveness of a drug such as an antimicrobial or an antineoplastic in curing a disease or condition. When the drug is not intended to kill or inhibit a pathogen, then the term is equivalent to dosage failure or drug tolerance. More commonly, the term is used...
. Still another route to make CPT’s lipophilic is to introduce lipophilic substituents, such as iminomethyl or oxyiminomethyl moieties. One of the most potent compounds is the oxyiminomethyl derivative ST1481 that has the advantage to overcome drug resistance caused by transport systems.
Basic nitrogen
Nitrogen
Nitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
in a carbon chain at position 7 makes the compound more hydrophilic and hence more water-soluble. For example is a derivate called CKD-602, which is a potent topo I inhibitor and successfully overcomes the poor water solubility and toxicity seen with CPT.
Considerably greater activity can be achieved by putting electron-withdrawing groups like amino, nitro
Nitro compound
Nitro compounds are organic compounds that contain one or more nitro functional groups . They are often highly explosive, especially when the compound contains more than one nitro group and is impure. The nitro group is one of the most common explosophores used globally...
, bromo or chloro at position 9 and 10 and hydroxyl group at position 10 or 11. But these compounds are relatively insoluble in aqueous solutions, which causes difficulty in administrations. Methoxy
Methoxy
In chemistry , methoxy refers to the functional group consisting of a methyl group bound to oxygen. This alkoxy group has the formula O–CH3.The word is used in organic nomenclature usually to describe an ether...
group at both position 10 and 11 simultaneously leads to inactivity.
Hexacyclic CPT analogues
Hexacyclic CPT analogues have shown great potency. For example methylenedioxyMethylenedioxy
Methylenedioxy in the field of chemistry, particularly in organic chemistry, is the name for a functional group with the structural formula R-O-CH2-O-R' which is connected to the rest of a molecule by two chemical bonds. The methylenedioxy group consists of two oxygen atoms connected to a methylene...
or ethylenedioxy group connected between 10 and 11 form a 5 or 6 membered ring which leads to more water-soluble derivates and increased potency. Researches have shown that ethylenedioxy analogues are less potent than methylenedioxy. The reason is the unfavorable steric interactions of ethylenedioxy analogues with the enzyme.
Adding amino or chloro group at 9th position or chloromethyl group at 7th position to these 10, 11-methylenedioxy or ethylenedioxy analogues results in compounds with even greater cytotoxicity but weaker solubility in water. To yield 10, 11-methylenedioxy or ethylenedioxy analogues with good water solubility a good way is to introduce a water solubilising substituent at position 7. Lurtotecan meets those requirements; it’s a 10, 11-ethylenedioxy analogue with a 4-methylpiperazino-methylene at position 7 and has shown a great potency in clinical researches.
A ring can also be formed between position 7 and 9, like position 10 and 11. That gives new opportunities to make water-soluble derivatives [5]. These hexacyclic CPT become more active when electron-withdrawing groups are put in position 11 and methyl or amino groups at 10. Exatecan is an example of hexacyclic CPT that has a 6 membered ring over position 7 and 9, and is 10-methyl, 11-fluoro substituted [4]. It is water-soluble and more potent than topotecan.
C- and D-ring modification
The D- and C-rings have an essential role in the antitumor activity. Replacement in any position results in much less potent compound than parent compound in other cytotoxicity assay.E-ring modifications
The E-ring doesn’t allow many structural changes without losing CPT activity. One possible replacement is changing the hydroxyl group to Cl, F or Br because their polarizabilityPolarizability
Polarizability is the measure of the change in a molecule's electron distribution in response to an applied electric field, which can also be induced by electric interactions with solvents or ionic reagents. It is a property of matter...
is sufficient to stabilize the enzyme-complex.
Another possible modification is to insert a methylene between hydroxyl and lactone on the E-ring yielding a seven membered β-hydroxylactone group, so-called homocamptothecin (hCPT). The hCPT’s hydroxyl has less inductive effect
Inductive effect
In chemistry and physics, the inductive effect is an experimentally observable effect of the transmission of charge through a chain of atoms in a molecule by electrostatic induction...
on the carboxyl group which makes the lactone very reactive. This enhances the interaction of the free hydroxyl group optimally with topo I and the covalent complex that forms in its presence are more stable. The E-ring of hCPT opens more slowly and the opening is irreversible
Irreversibility
In science, a process that is not reversible is called irreversible. This concept arises most frequently in thermodynamics, as applied to processes....
. hCPTs exhibit enhanced human plasma stability because of decreased protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
binding and more affinity for red blood cells than CPT.
CPT analogues
Since the discovery of CPT many analogues have been synthesized. Below is a schematic view of the CPT analogues that have been mentioned in the text above.| Analogue | R1 | R2 | R3 | R4 |
|---|---|---|---|---|
| Topotecan (Hycamtin) | -H | CH2N(CH3)2 | -OH | H |
| Irinotecan (CPT-11, Camptosar) | CH2CH3 | H | H | |
| DB 67 (AR67) | H | OH | H | |
| BNP 1350 | CH2CH2Si(CH3)3 | H | H | H |
| Exatecan Exatecan Exatecan is a drug which is an analogue of camptothecin.... |
CH3 | F | ||
| Lurtotecan Lurtotecan Lurtotecan is an analogue of camptothecin.... |
H | |||
| ST 1481 | CH=NOC(CH3)3 | H | H | H |
| CKD 602 | CH2CH2NHCH(CH3)2 | H | H | H |
CPT is linked to a cyclodextrin
Cyclodextrin
Cyclodextrins are a family of compounds made up of sugar molecules bound together in a ring ....
-based polymer to form the investigational anti-cancer drug CRLX101.