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Chemical Structure| 728033-96-3 Chemical Structure| 728033-96-3

Structure of OSI-930
CAS No.: 728033-96-3

Chemical Structure| 728033-96-3

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OSI-930 is a potent inhibitor of Kit, KDR and CSF-1R with IC50 of 80 nM, 9 nM and 15 nM, respectively and also potent to Flt-1, c-Raf and Lck and low activity against PDGFRα/β, Flt-3 and Abl.

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Product Details of OSI-930

CAS No. :728033-96-3
Formula : C22H16F3N3O2S
M.W : 443.44
SMILES Code : O=C(C1=C(NCC2=CC=NC3=CC=CC=C23)C=CS1)NC4=CC=C(OC(F)(F)F)C=C4
MDL No. :MFCD11100358
InChI Key :FGTCROZDHDSNIO-UHFFFAOYSA-N
Pubchem ID :9868037

Safety of OSI-930

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of OSI-930

RTK

Isoform Comparison

Biological Activity

Target
  • VEGFR1

    FLT1, IC50:8 nM

  • VEGFR2

    KDR, IC50:9 nM

  • c-Kit

    Kit, IC50:80 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
ABCG2-482-T7 10 µM 2 hours To determine the effect of VKJP1 and VKJP3 on intracellular accumulation of [3H]-mitoxantrone. Results showed that VKJP1 and VKJP3 significantly increased the intracellular accumulation of [3H]-mitoxantrone in ABCG2-482-T7 cells. Biochem Pharmacol. 2012 Sep 15;84(6):766-74.
ABCG2-482-R2 10 µM 2 hours To determine the effect of VKJP1 and VKJP3 on intracellular accumulation of [3H]-mitoxantrone. Results showed that VKJP1 and VKJP3 significantly increased the intracellular accumulation of [3H]-mitoxantrone in ABCG2-482-R2 cells. Biochem Pharmacol. 2012 Sep 15;84(6):766-74.
HEK293/pcDNA3.1 10 µM 72 hours To evaluate the effect of VKJP1 and VKJP3 on ABCG2 expression. Results showed that the protein levels of ABCG2 were not significantly altered by VKJP1 or VKJP3 treatment for up to 72 h. Biochem Pharmacol. 2012 Sep 15;84(6):766-74.
Recombinant cytochrome P450 3A4 24 µM 30 minutes To investigate the mechanism-based inactivation of P450 3A4 by OSI-930, results showed time- and concentration-dependent inactivation with KI=24 µM and kinact=0.04 min−1. Drug Metab Dispos. 2011 Feb;39(2):345-50.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Nude mice GEO colorectal xenograft model Oral gavage 200 mg/kg Once daily for 7 days OSI-930 reduced vessel sprouting and caused substantial vascular regression in tumors Cancer Res. 2011 Mar 1;71(5):1573-83.

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.26mL

0.45mL

0.23mL

11.28mL

2.26mL

1.13mL

22.55mL

4.51mL

2.26mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[1]Lin HL, Zhang H, et al. Inactivation of cytochrome P450 (P450) 3A4 but not P450 3A5 by OSI-930, a thiophene-containing anticancer drug. Drug Metab Dispos. 2011 Feb;39(2):345-50.

[2]Garton AJ, Crew AP, et al. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 2006 Jan 15;66(2):1015-24.

[3]Petti F, Thelemann A, Kahler J, McCormack S, Castaldo L, Hunt T, Nuwaysir L, Zeiske L, Haack H, Sullivan L, Garton A, Haley JD. Temporal quantitation of mutant Kit tyrosine kinase signaling attenuated by a novel thiophene kinase inhibitor OSI-930. Mol Cancer Ther. 2005 Aug;4(8):1186-97. doi: 10.1158/1535-7163.MCT-05-0114. PMID: 16093434.

[4]Patel JP, Kuang YH, Chen ZS, Korlipara VL. Inhibition of c-Kit, VEGFR-2 (KDR), and ABCG2 by analogues of OSI-930. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6495-9. doi: 10.1016/j.bmcl.2011.08.070. Epub 2011 Aug 22. PMID: 21920748.

[5]Garton AJ, Crew AP, Franklin M, Cooke AR, Wynne GM, Castaldo L, Kahler J, Winski SL, Franks A, Brown EN, Bittner MA, Keily JF, Briner P, Hidden C, Srebernak MC, Pirrit C, O'Connor M, Chan A, Vulevic B, Henninger D, Hart K, Sennello R, Li AH, Zhang T, Richardson F, Emerson DL, Castelhano AL, Arnold LD, Gibson NW. OSI-930: a novel selective inhibitor of Kit and kinase insert domain receptor tyrosine kinases with antitumor activity in mouse xenograft models. Cancer Res. 2006 Jan 15;66(2):1015-24. doi: 10.1158/0008-5472.CAN-05-2873. PMID: 16424037.

 

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