WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406164
CAS#: 260415-63-2
Description: PD-173955 is a src tyrosine kinase inhibitor. PD173955 inhibited Bcr-Abl-dependent cell growth. PD173955 showed cell cycle arrest in G(1). PD173955 has an IC(50) of 1-2 nM in kinase inhibition assays of Bcr-Abl, and in cellular growth assays it inhibits Bcr-Abl-dependent substrate tyrosine phosphorylation. PD173955 inhibited kit ligand-dependent c-kit autophosphorylation (IC(50) = approximately 25 nM) and kit ligand-dependent proliferation of M07e cells (IC(50) = 40 nM) but had a lesser effect on interleukin 3-dependent (IC(50) = 250 nM) or granulocyte macrophage colony-stimulating factor (IC(50) = 1 microM)-dependent cell growth.
MedKoo Cat#: 406164
Name: PD-173955
CAS#: 260415-63-2
Chemical Formula: C21H16Cl2N4OS
Exact Mass: 442.0422
Molecular Weight: 443.3489
Elemental Analysis: C, 56.89; H, 3.64; Cl, 15.99; N, 12.64; O, 3.61; S, 7.23
Synonym: PD173955; PD 173955; PD173955.
IUPAC/Chemical Name: 6-(2,6-dichlorophenyl)-8-methyl-2-((3-(methylthio)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one
InChi Key: VAARYSWULJUGST-UHFFFAOYSA-N
InChi Code: InChI=1S/C21H16Cl2N4OS/c1-27-19-12(9-15(20(27)28)18-16(22)7-4-8-17(18)23)11-24-21(26-19)25-13-5-3-6-14(10-13)29-2/h3-11H,1-2H3,(H,24,25,26)
SMILES Code: O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3=CN=C(NC4=CC=CC(SC)=C4)N=C3N1C
Appearance: white solid powder
Purity: >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).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 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: 2934.99.9001
| Biological target: | PD173955 is src family-selective tyrosine kinase inhibitor with IC50 of ~22 nM for for Src, Yes and Abl kinase. |
| In vitro activity: | This study studied the effects of PD173955, a novel src family-selective tyrosine kinase inhibitor, on cancer cell lines and found that it has significant antiproliferative activity due to a potent arrest of mitotic progression. The mitotic block occurs after chromosome condensation in prophase, before spindle assembly and without loss of cyclin A and B kinase activities. This effect is seen in cancer cell lines of all types with low or high activities of src kinases as well as in untransformed cell lines. Reference: Cancer Res. 1999 Dec 15;59(24):6145-52. https://pubmed.ncbi.nlm.nih.gov/10626805/ |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 1.0 | 2.26 | |
| DMSO | 5.5 | 12.41 |
The following data is based on the product molecular weight 443.3489 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.
| 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 |
| Formulation protocol: | 1. Windham TC, Parikh NU, Siwak DR, Summy JM, McConkey DJ, Kraker AJ, Gallick GE. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002 Nov 7;21(51):7797-807. doi: 10.1038/sj.onc.1205989. PMID: 12420216. 2. Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res. 1999 Dec 15;59(24):6145-52. PMID: 10626805. |
| In vitro protocol: | 1. Windham TC, Parikh NU, Siwak DR, Summy JM, McConkey DJ, Kraker AJ, Gallick GE. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002 Nov 7;21(51):7797-807. doi: 10.1038/sj.onc.1205989. PMID: 12420216. 2. Moasser MM, Srethapakdi M, Sachar KS, Kraker AJ, Rosen N. Inhibition of Src kinases by a selective tyrosine kinase inhibitor causes mitotic arrest. Cancer Res. 1999 Dec 15;59(24):6145-52. PMID: 10626805. |
| In vivo protocol: | TBD |
1: Kraus GA, Gupta V, Mokhtarian M, Mehanovic S, Nilsen-Hamilton M. New effective inhibitors of the Abelson kinase. Bioorg Med Chem. 2010 Sep 1;18(17):6316-21. doi: 10.1016/j.bmc.2010.07.021. Epub 2010 Jul 14. PubMed PMID: 20674368.
2: Sylvester JE, Kron SJ. A bead-based activity screen for small-molecule inhibitors of signal transduction in chronic myelogenous leukemia cells. Mol Cancer Ther. 2010 May;9(5):1469-81. doi: 10.1158/1535-7163.MCT-10-0157. Epub 2010 Apr 27. PubMed PMID: 20423990; PubMed Central PMCID: PMC2868067.
3: Crespo A, Fernández A. Induced disorder in protein-ligand complexes as a drug-design strategy. Mol Pharm. 2008 May-Jun;5(3):430-7. doi: 10.1021/mp700148h. Epub 2008 Feb 16. Erratum in: Mol Pharm. 2008 Jul-Aug;5(4):680. Mol Pharm. 2010 Feb 1;7(1):306. Mol Pharm. 2010 Oct 4;7(5):1877. PubMed PMID: 18278867.
4: Gunby RH, Ahmed S, Sottocornola R, Gasser M, Redaelli S, Mologni L, Tartari CJ, Belloni V, Gambacorti-Passerini C, Scapozza L. Structural insights into the ATP binding pocket of the anaplastic lymphoma kinase by site-directed mutagenesis, inhibitor binding analysis, and homology modeling. J Med Chem. 2006 Sep 21;49(19):5759-68. PubMed PMID: 16970400.
5: Caligiuri M, Molz L, Liu Q, Kaplan F, Xu JP, Majeti JZ, Ramos-Kelsey R, Murthi K, Lievens S, Tavernier J, Kley N. MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells. Chem Biol. 2006 Jul;13(7):711-22. PubMed PMID: 16873019.
6: Verkhivker GM. Imprint of evolutionary conservation and protein structure variation on the binding function of protein tyrosine kinases. Bioinformatics. 2006 Aug 1;22(15):1846-54. Epub 2006 May 23. PubMed PMID: 16720585.
7: Liu L, D'Mello SR. Phosphorylation of IkappaB-beta is necessary for neuronal survival. J Biol Chem. 2006 Jan 20;281(3):1506-15. Epub 2005 Nov 11. PubMed PMID: 16286457.
8: O'Hare T, Pollock R, Stoffregen EP, Keats JA, Abdullah OM, Moseson EM, Rivera VM, Tang H, Metcalf CA 3rd, Bohacek RS, Wang Y, Sundaramoorthi R, Shakespeare WC, Dalgarno D, Clackson T, Sawyer TK, Deininger MW, Druker BJ. Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML. Blood. 2004 Oct 15;104(8):2532-9. Epub 2004 Jul 15. PubMed PMID: 15256422.
9: Cowan-Jacob SW, Guez V, Fendrich G, Griffin JD, Fabbro D, Furet P, Liebetanz J, Mestan J, Manley PW. Imatinib (STI571) resistance in chronic myelogenous leukemia: molecular basis of the underlying mechanisms and potential strategies for treatment. Mini Rev Med Chem. 2004 Mar;4(3):285-99. Review. PubMed PMID: 15032675.
10: Strife A, Wisniewski D, Liu C, Lambek CL, Darzynkiewicz Z, Silver RT, Clarkson B. Direct evidence that Bcr-Abl tyrosine kinase activity disrupts normal synergistic interactions between Kit ligand and cytokines in primary primitive progenitor cells. Mol Cancer Res. 2003 Jan;1(3):176-85. PubMed PMID: 12556557.
