WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 202231

CAS#: 477575-56-7

Description: PHA665752 is a potent and selective inhibitor of c-Met/HGF/SF (IC50 values are 9, 68, 200, 1400, 3000, 3800 and 6000 nM for MET, Ron, Flk-1, c-abl, FGFR1, EGFR and c-src respectively). PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells. PHA-665752 reverses lung premalignancy induced by mutant K-ras. PHA-665752 induced apoptosis of a lung adenocarcinoma cell line derived from Kras(LA1) mice (LKR-13) and a murine lung endothelial cell line (MEC). PHA-665752 inhibited lung tumorigenesis in Kras(LA1) mice and may provide a novel therapeutic approach to the prevention of K-ras-mutant NSCLC.

Chemical Structure

CAS# 477575-56-7

Theoretical Analysis

MedKoo Cat#: 202231
Name: PHA-665752
CAS#: 477575-56-7
Chemical Formula: C32H34Cl2N4O4S
Exact Mass: 640.16778
Molecular Weight: 641.61
Elemental Analysis: C, 59.90; H, 5.34; Cl, 11.05; N, 8.73; O, 9.97; S, 5.00

Size Price Shipping out time Quantity
5mg USD 210 2 Weeks
10mg USD 360 2 Weeks
25g USD 685 2 Weeks
Inquire bulk and customized quantity

Pricing updated 2021-03-08. Prices are subject to change without notice.

PHA-665752 purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Synonym: PHA665752; PHA 665752; PHA 665752

IUPAC/Chemical Name: (R,Z)-5-((2,6-dichlorobenzyl)sulfonyl)-3-((3,5-dimethyl-4-(2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl)-1H-pyrrol-2-yl)methylene)indolin-2-one


InChi Code: InChI=1S/C32H34Cl2N4O4S/c1-19-29(35-20(2)30(19)32(40)38-14-6-7-21(38)17-37-12-3-4-13-37)16-24-23-15-22(10-11-28(23)36-31(24)39)43(41,42)18-25-26(33)8-5-9-27(25)34/h5,8-11,15-16,21,35H,3-4,6-7,12-14,17-18H2,1-2H3,(H,36,39)/b24-16-/t21-/m1/s1

SMILES Code: O=C1NC2=C(C=C(S(=O)(CC3=C(Cl)C=CC=C3Cl)=O)C=C2)/C1=C/C4=C(C)C(C(N5[C@@H](CN6CCCC6)CCC5)=O)=C(C)N4

Solid powder

>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

soluble in DMSO

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code:

Handling Instructions:

Preparing Stock Solutions

The following data is based on the product molecular weight 641.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Select a batch to recalculate based on the batch molecular weight:
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL

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1: Wang D, Saga Y, Sato N, Nakamura T, Takikawa O, Mizukami H, Matsubara S, Fujiwara H. The hepatocyte growth factor antagonist NK4 inhibits indoleamine-2,3-dioxygenase expression via the c-Met-phosphatidylinositol 3-kinase-AKT signaling pathway. Int J Oncol. 2016 Jun;48(6):2303-9. doi: 10.3892/ijo.2016.3486. Epub 2016 Apr 14. PubMed PMID: 27082119; PubMed Central PMCID: PMC4863924.

2: Yoon YS, Lee YJ, Choi YH, Park YM, Kang JL. Macrophages programmed by apoptotic cells inhibit epithelial-mesenchymal transition in lung alveolar epithelial cells via PGE2, PGD2, and HGF. Sci Rep. 2016 Feb 15;6:20992. doi: 10.1038/srep20992. PubMed PMID: 26875548; PubMed Central PMCID: PMC4753481.

3: Jagoda EM, Bhattacharyya S, Kalen J, Riffle L, Leeder A, Histed S, Williams M, Wong KJ, Xu B, Szajek LP, Elbuluk O, Cecchi F, Raffensperger K, Golla M, Bottaro DP, Choyke P. Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse Models with a [99mTc] (AH-113018) or Cy 5** (AH-112543) Labeled Peptide. Mol Imaging. 2015;14:499-515. PubMed PMID: 26461980.

4: Xiang Q, Zhen Z, Deng DY, Wang J, Chen Y, Li J, Zhang Y, Wang F, Chen N, Chen H, Chen Y. Tivantinib induces G2/M arrest and apoptosis by disrupting tubulin polymerization in hepatocellular carcinoma. J Exp Clin Cancer Res. 2015 Oct 12;34:118. doi: 10.1186/s13046-015-0238-2. PubMed PMID: 26458953; PubMed Central PMCID: PMC4603939.

5: Ahmed M, Kumar G, Moussa M, Wang Y, Rozenblum N, Galun E, Goldberg SN. Hepatic Radiofrequency Ablation-induced Stimulation of Distant Tumor Growth Is Suppressed by c-Met Inhibition. Radiology. 2016 Apr;279(1):103-17. doi: 10.1148/radiol.2015150080. Epub 2015 Sep 29. PubMed PMID: 26418615; PubMed Central PMCID: PMC4819900.

6: Sugano T, Seike M, Noro R, Soeno C, Chiba M, Zou F, Nakamichi S, Nishijima N, Matsumoto M, Miyanaga A, Kubota K, Gemma A. Inhibition of ABCB1 Overcomes Cancer Stem Cell-like Properties and Acquired Resistance to MET Inhibitors in Non-Small Cell Lung Cancer. Mol Cancer Ther. 2015 Nov;14(11):2433-40. doi: 10.1158/1535-7163.MCT-15-0050. Epub 2015 Sep 8. PubMed PMID: 26351321.

7: Komarowska I, Coe D, Wang G, Haas R, Mauro C, Kishore M, Cooper D, Nadkarni S, Fu H, Steinbruchel DA, Pitzalis C, Anderson G, Bucy P, Lombardi G, Breckenridge R, Marelli-Berg FM. Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release. Immunity. 2015 Jun 16;42(6):1087-99. doi: 10.1016/j.immuni.2015.05.014. Epub 2015 Jun 9. PubMed PMID: 26070483; PubMed Central PMCID: PMC4510150.

8: Chang CC, Hsieh TL, Tiong TY, Hsiao CH, Ji AT, Hsu WT, Lee OK, Ho JH. Regulation of metastatic ability and drug resistance in pulmonary adenocarcinoma by matrix rigidity via activating c-Met and EGFR. Biomaterials. 2015 Aug;60:141-50. doi: 10.1016/j.biomaterials.2015.04.058. Epub 2015 May 19. PubMed PMID: 26000960.

9: Steinway SN, Dang H, You H, Rountree CB, Ding W. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma. PLoS One. 2015 May 22;10(5):e0128159. doi: 10.1371/journal.pone.0128159. eCollection 2015. PubMed PMID: 26000702; PubMed Central PMCID: PMC4441360.

10: Rozenblum N, Zeira E, Bulvik B, Gourevitch S, Yotvat H, Galun E, Goldberg SN. Radiofrequency Ablation: Inflammatory Changes in the Periablative Zone Can Induce Global Organ Effects, including Liver Regeneration. Radiology. 2015 Aug;276(2):416-25. doi: 10.1148/radiol.15141918. Epub 2015 Mar 30. PubMed PMID: 25822472.

11: Sakamoto S, Inoue H, Ohba S, Kohda Y, Usami I, Masuda T, Kawada M, Nomoto A. New metastatic model of human small-cell lung cancer by orthotopic transplantation in mice. Cancer Sci. 2015 Apr;106(4):367-74. doi: 10.1111/cas.12624. Epub 2015 Feb 26. PubMed PMID: 25640943; PubMed Central PMCID: PMC4409879.

12: Nakamura M, Takahashi T, Matsui H, Baniwa Y, Takahashi S, Murayama SY, Serizawa H, Suzuki H, Hibi T. Alteration of angiogenesis in Helicobacter heilmannii-induced mucosa-associated lymphoid tissue lymphoma: interaction with c-Met and hepatocyte growth factor. J Gastroenterol Hepatol. 2014 Dec;29 Suppl 4:70-6. doi: 10.1111/jgh.12776. PubMed PMID: 25521737.

13: Deng XB, Xiao L, Wu Y, Jin F, Mossman B, Testa JR, Xiao GH. Inhibition of mesothelioma cancer stem-like cells with adenovirus-mediated NK4 gene therapy. Int J Cancer. 2015 Jul 15;137(2):481-90. doi: 10.1002/ijc.29391. Epub 2014 Dec 27. PubMed PMID: 25501304; PubMed Central PMCID: PMC4428975.

14: Petti C, Picco G, Martelli ML, Trisolini E, Bucci E, Perera T, Isella C, Medico E. Truncated RAF kinases drive resistance to MET inhibition in MET-addicted cancer cells. Oncotarget. 2015 Jan 1;6(1):221-33. PubMed PMID: 25473895; PubMed Central PMCID: PMC4381590.

15: Yun C, Gang L, Rongmin G, Xu W, Xuezhi M, Huanqiu C. Essential role of Her3 in two signaling transduction patterns: Her2/Her3 and MET/Her3 in proliferation of human gastric cancer. Mol Carcinog. 2015 Dec;54(12):1700-9. doi: 10.1002/mc.22241. Epub 2014 Nov 14. PubMed PMID: 25400108.

16: Calles A, Kwiatkowski N, Cammarata BK, Ercan D, Gray NS, Jänne PA. Tivantinib (ARQ 197) efficacy is independent of MET inhibition in non-small-cell lung cancer cell lines. Mol Oncol. 2015 Jan;9(1):260-9. doi: 10.1016/j.molonc.2014.08.011. Epub 2014 Aug 29. PubMed PMID: 25226813.

17: Pennacchietti S, Cazzanti M, Bertotti A, Rideout WM 3rd, Han M, Gyuris J, Perera T, Comoglio PM, Trusolino L, Michieli P. Microenvironment-derived HGF overcomes genetically determined sensitivity to anti-MET drugs. Cancer Res. 2014 Nov 15;74(22):6598-609. doi: 10.1158/0008-5472.CAN-14-0761. Epub 2014 Sep 12. PubMed PMID: 25217525.

18: Ali NA, Wu J, Hochgräfe F, Chan H, Nair R, Ye S, Zhang L, Lyons RJ, Pinese M, Lee HC, Armstrong N, Ormandy CJ, Clark SJ, Swarbrick A, Daly RJ. Profiling the tyrosine phosphoproteome of different mouse mammary tumour models reveals distinct, model-specific signalling networks and conserved oncogenic pathways. Breast Cancer Res. 2014 Sep 9;16(5):437. doi: 10.1186/s13058-014-0437-3. PubMed PMID: 25200860; PubMed Central PMCID: PMC4303118.

19: Tsai PC, Chu CL, Chiu CC, Chang LS, Lin SR. Cardiotoxin III suppresses hepatocyte growth factor-stimulated migration and invasion of MDA-MB-231 cells. Cell Biochem Funct. 2014 Aug;32(6):485-95. doi: 10.1002/cbf.3041. Epub 2014 Jun 26. PubMed PMID: 24964901.

20: Furcht CM, Buonato JM, Skuli N, Mathew LK, Muñoz Rojas AR, Simon MC, Lazzara MJ. Multivariate signaling regulation by SHP2 differentially controls proliferation and therapeutic response in glioma cells. J Cell Sci. 2014 Aug 15;127(Pt 16):3555-67. doi: 10.1242/jcs.150862. Epub 2014 Jun 20. PubMed PMID: 24951116; PubMed Central PMCID: PMC4132393.

Additional Information