Rubitecan

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Rubitecan
Accession Number
DB06159
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
  • 9-nitrocamptothecin
  • 9NC
  • Camptogen
  • RF-2000
External IDs
RFS 2000 / RFS-2000 / RFS2000
International/Other Brands
Orathecin (Supergen)
Categories
UNII
H19C446XXB
CAS number
91421-42-0
Weight
Average: 393.3496
Monoisotopic: 393.096085227
Chemical Formula
C20H15N3O6
InChI Key
GXSOIDVPIMWEQT-FQEVSTJZSA-N
InChI
InChI=1S/C20H15N3O6/c1-2-20(26)13-7-15-16-11(8-22(15)18(24)12(13)9-29-19(20)25)17(23(27)28)10-5-3-4-6-14(10)21-16/h3-7,26H,2,8-9H2,1H3/t20-/m0/s1
IUPAC Name
(19S)-19-ethyl-19-hydroxy-10-nitro-17-oxa-3,13-diazapentacyclo[11.8.0.0²,¹¹.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
SMILES
CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=C(C4=CC=CC=C4N=C13)[N+]([O-])=O)C2=O

Pharmacology

Indication

Investigated for use/treatment in pancreatic cancer, leukemia (unspecified), melanoma, ovarian cancer, and cancer/tumors (unspecified).

Pharmacodynamics
Not Available
Mechanism of action

Rubitecan prevents DNA from unwinding during replication via DNA topoisomerase 1, therefore interfering with tumor growth.

TargetActionsOrganism
UDNA topoisomerase 1Not AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
PubChem Compound
11954380
ChemSpider
10128675
Wikipedia
Rubitecan

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentTumors1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
2CompletedTreatmentBladder Cancers / Transitional Cell Cancer of the Renal Pelvis and Ureter / Urethral Cancer1
2CompletedTreatmentBrain and Central Nervous System Tumors1
2CompletedTreatmentCancer of the Ovary1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentGastrointestinal Stromal Tumors / Sarcomas / Small Intestine Cancer1
2CompletedTreatmentLung Cancers2
2CompletedTreatmentMelanoma (Skin)1
2Unknown StatusTreatmentColorectal Cancers1
2Unknown StatusTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2WithdrawnTreatmentCancer of the Ovary / Primary Peritoneal Cavity Cancer1
2, 3TerminatedTreatmentMalignant Neoplasm of Pancreas1
3Unknown StatusTreatmentMalignant Neoplasm of Pancreas3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.254 mg/mLALOGPS
logP2.25ALOGPS
logP1.16ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)11.71ChemAxon
pKa (Strongest Basic)-0.23ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area125.55 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity101.82 m3·mol-1ChemAxon
Polarizability38.69 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7977
Blood Brain Barrier-0.6125
Caco-2 permeable-0.8307
P-glycoprotein substrateSubstrate0.5853
P-glycoprotein inhibitor INon-inhibitor0.7775
P-glycoprotein inhibitor IINon-inhibitor0.9611
Renal organic cation transporterNon-inhibitor0.8838
CYP450 2C9 substrateNon-substrate0.8475
CYP450 2D6 substrateNon-substrate0.8388
CYP450 3A4 substrateSubstrate0.6054
CYP450 1A2 substrateInhibitor0.6135
CYP450 2C9 inhibitorNon-inhibitor0.647
CYP450 2D6 inhibitorNon-inhibitor0.8503
CYP450 2C19 inhibitorNon-inhibitor0.6043
CYP450 3A4 inhibitorInhibitor0.6262
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6372
Ames testAMES toxic0.7389
CarcinogenicityNon-carcinogens0.6422
BiodegradationNot ready biodegradable0.9971
Rat acute toxicity2.7520 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9616
hERG inhibition (predictor II)Non-inhibitor0.862
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-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).
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Camptothecins
Sub Class
Not Available
Direct Parent
Camptothecins
Alternative Parents
Nitroquinolines and derivatives / Pyranopyridines / Nitroaromatic compounds / Pyridinones / Benzenoids / Tertiary alcohols / Heteroaromatic compounds / Carboxylic acid esters / Lactones / Lactams
show 11 more
Substituents
Camptothecin / Nitroquinoline / Pyranopyridine / Quinoline / Nitroaromatic compound / Pyridinone / Pyridine / Benzenoid / Heteroaromatic compound / Tertiary alcohol
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific Function
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Chedid S, Rivera E, Frye DK, Ibrahim N, Esteva F, Valero V, Hortobagyi G, Mettinger KL, Cristofanilli M: Minimal clinical benefit of single agent Orathecin (Rubitecan) in heavily pretreated metastatic breast cancer. Cancer Chemother Pharmacol. 2006 Apr;57(4):540-4. Epub 2005 Sep 29. [PubMed:16193332]

Drug created on March 19, 2008 10:14 / Updated on November 02, 2018 06:14