OSI-7836

Identification

Generic Name: OSI-7836
DrugBank Accession Number: DB05837
Background: 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.
Type: Small Molecule
Groups: Investigational
Structure: MOL SDF PDB SMILES InChI

Similar Structures
Structure for OSI-7836 (DB05837)
Synonyms: Not Available

Pharmacology

Indication: Investigated for use/treatment in solid tumors.

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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
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Toxicity: Not Available
Pathways: Not Available
Pharmacogenomic Effects/ADRs: Not Available

Interactions

Drug Interactions: This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions: Not Available

Chemical Identifiers

UNII: YCO2764D5Z
CAS number: Not Available
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

References

General References

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. [Article]
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. [Article]

External Links

PubChem Compound: 3037115
PubChem Substance: 175427042
ChemSpider: 2300942

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

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

Property	Value	Source
Water Solubility	9.58 mg/mL	ALOGPS
logP	-1.7	ALOGPS
logP	-2.4	Chemaxon
logS	-1.5	ALOGPS
pKa (Strongest Acidic)	9.28	Chemaxon
pKa (Strongest Basic)	7.48	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	7	Chemaxon
Hydrogen Donor Count	5	Chemaxon
Polar Surface Area	131.77 Å²	Chemaxon
Rotatable Bond Count	2	Chemaxon
Refractivity	64.89 m³·mol^-1	Chemaxon
Polarizability	25.55 Å³	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	No	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.6198
Blood Brain Barrier	+	0.7245
Caco-2 permeable	-	0.6802
P-glycoprotein substrate	Non-substrate	0.9083
P-glycoprotein inhibitor I	Non-inhibitor	0.9511
P-glycoprotein inhibitor II	Non-inhibitor	0.9284
Renal organic cation transporter	Non-inhibitor	0.9536
CYP450 2C9 substrate	Non-substrate	0.7271
CYP450 2D6 substrate	Non-substrate	0.8236
CYP450 3A4 substrate	Non-substrate	0.602
CYP450 1A2 substrate	Non-inhibitor	0.8368
CYP450 2C9 inhibitor	Non-inhibitor	0.8099
CYP450 2D6 inhibitor	Non-inhibitor	0.8896
CYP450 2C19 inhibitor	Non-inhibitor	0.7708
CYP450 3A4 inhibitor	Non-inhibitor	0.719
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8711
Ames test	Non AMES toxic	0.5619
Carcinogenicity	Non-carcinogens	0.7938
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	2.4518 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9983
hERG inhibition (predictor II)	Non-inhibitor	0.8357

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)