OSI-7836

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
OSI-7836
Accession Number
DB05837
Type
Small Molecule
Groups
Investigational
Description

OSI-7836 is a member of the nucleoside class of cytotoxic drugs of which gemcitabine is the market leader. OSI Pharmaceuticals develops OSI-7836 as a next-generation gemcitabine. The anti-tumor activity of OSI-7836 appeares to be less schedule dependent than gemcitabine. It is also more active than ara-C (another clinically used nucleoside analog) in all nine models and more active than either paclitaxel or cisplatin in the two lung xenograft models tested. This drug shows no unexpected toxicities; those observed appeared to be similar to other nucleoside agents.

Structure
Thumb
Synonyms
Not Available
Categories
UNII
Not Available
CAS number
Not Available
Weight
Average: 311.743
Monoisotopic: 311.03426897
Chemical Formula
C9H14ClN3O5S
InChI Key
RCWYXGAOCMUXHG-ZXBIKLPVSA-N
InChI
InChI=1S/C9H13N3O5S.ClH/c10-5-1-2-12(8(18)11-5)9(16)7(15)6(14)4(3-13)17-9;/h1-2,4,6-7,13-16H,3H2,(H2,10,11,18);1H/t4-,6-,7+,9-;/m1./s1
IUPAC Name
4-amino-1-[(2R,3S,4S,5R)-2,3,4-trihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,2-dihydropyrimidine-2-thione hydrochloride
SMILES
Cl.NC1=NC(=S)N(C=C1)[C@]1(O)O[C@H](CO)[C@@H](O)[C@@H]1O

Pharmacology

Indication

Investigated for use/treatment in solid tumors.

Pharmacodynamics
Not Available
Mechanism of action

OSI-7836 appears to have a different mechanism of tumor growth inhibition blocking the cell division cycle at a different point (the G2 phase) than gemcitabine. The mechanism of action involves phosphorylation to the triphosphate form followed by incorporation into cellular DNA, leading to cell death.

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
  1. Richardson F, Black C, Richardson K, Franks A, Wells E, Karimi S, Sennello G, Hart K, Meyer D, Emerson D, Brown E, LeRay J, Nilsson C, Tomkinson B, Bendele R: Incorporation of OSI-7836 into DNA of Calu-6 and H460 xenograft tumors. Cancer Chemother Pharmacol. 2005 Mar;55(3):213-21. Epub 2004 Nov 16. [PubMed:15592840]
  2. Roy AM, Tiwari KN, Parker WB, Secrist JA 3rd, Li R, Qu Z: Antiangiogenic activity of 4'-thio-beta-D-arabinofuranosylcytosine. Mol Cancer Ther. 2006 Sep;5(9):2218-24. [PubMed:16985055]
External Links
PubChem Compound
3037115
PubChem Substance
175427042
ChemSpider
2300942

Clinical Trials

Clinical Trials
Not Available

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
logP-2.3ChemAxon
pKa (Strongest Acidic)9.27ChemAxon
pKa (Strongest Basic)-0.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area131.77 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity64.89 m3·mol-1ChemAxon
Polarizability25.59 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6198
Blood Brain Barrier+0.7245
Caco-2 permeable-0.6802
P-glycoprotein substrateNon-substrate0.9083
P-glycoprotein inhibitor INon-inhibitor0.9511
P-glycoprotein inhibitor IINon-inhibitor0.9284
Renal organic cation transporterNon-inhibitor0.9536
CYP450 2C9 substrateNon-substrate0.7271
CYP450 2D6 substrateNon-substrate0.8236
CYP450 3A4 substrateNon-substrate0.602
CYP450 1A2 substrateNon-inhibitor0.8368
CYP450 2C9 inhibitorNon-inhibitor0.8099
CYP450 2D6 inhibitorNon-inhibitor0.8896
CYP450 2C19 inhibitorNon-inhibitor0.7708
CYP450 3A4 inhibitorNon-inhibitor0.719
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8711
Ames testNon AMES toxic0.5619
CarcinogenicityNon-carcinogens0.7938
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.4518 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9983
hERG inhibition (predictor II)Non-inhibitor0.8357
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 pyrimidine nucleosides. These are compounds comprising a pyrimidine base attached to a ribosyl or deoxyribosyl moiety.
Kingdom
Organic compounds
Super Class
Nucleosides, nucleotides, and analogues
Class
Pyrimidine nucleosides
Sub Class
Not Available
Direct Parent
Pyrimidine nucleosides
Alternative Parents
Pentoses / Pyrimidinethiones / Aminopyrimidines and derivatives / Imidolactams / Hydropyrimidines / Tetrahydrofurans / Heteroaromatic compounds / Secondary alcohols / Alkanolamines / Polyols
show 8 more
Substituents
Pyrimidine nucleoside / Pentose monosaccharide / Aminopyrimidine / Pyrimidinethione / Hydropyrimidine / Monosaccharide / Imidolactam / Pyrimidine / Heteroaromatic compound / Tetrahydrofuran
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Drug created on November 18, 2007 11:28 / Updated on June 04, 2019 06:20