PD180970 | CAS#287204-45-9 | Bcr-Abl inhibitor

MedKoo Cat#: 406175 | Name: PD180970

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Description:

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

PD180970 is a novel Bcr-Abl inhbitor. PD180970 inhibited in vivo tyrosine phosphorylation of p210Bcr-Abl (IC50 = 170 nM) and the p210BcrAbl substrates Gab2 and CrkL (IC50 = 80 nM) in human K562 chronic myelogenous leukemic cells. In vitro, PD180970 potently inhibited autophosphorylation of p210Bcr-Abl (IC50 = 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death. PD180970 is among the most potent inhibitors of the p210Bcr-Abl tyrosine kinase, which is present in almost all cases of human chronic myelogenous leukemia. PD180970 is a promising candidate as a novel therapeutic agent for Bcr-Abl-positive leukemia.

Chemical Structure

PD180970

CAS#287204-45-9

Theoretical Analysis

MedKoo Cat#: 406175

Name: PD180970

CAS#: 287204-45-9

Chemical Formula: C21H15Cl2FN4O

Exact Mass: 428.0607

Molecular Weight: 429.28

Elemental Analysis: C, 58.76; H, 3.52; Cl, 16.52; F, 4.43; N, 13.05; O, 3.73

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 350.00	2 Weeks
50mg	USD 950.00	2 Weeks

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Synonym

PD180970; PD180970; PD180970; PF1515965.

IUPAC/Chemical Name

6-(2,6-Dichlorophenyl)-2-[(4-fluoro-3-methylphenyl)amino]-8-methyl-pyrido[2,3-d]pyrimidin-7(8H)-one

InChi Key

SLCFEJAMCRLYRG-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H15Cl2FN4O/c1-11-8-13(6-7-17(11)24)26-21-25-10-12-9-14(20(29)28(2)19(12)27-21)18-15(22)4-3-5-16(18)23/h3-10H,1-2H3,(H,25,26,27)

SMILES Code

O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3=CN=C(NC4=CC=C(F)C(C)=C4)N=C3N1C

Appearance

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

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

PD180970 is a highly potent and ATP-competitive p210Bcr-Abl kinase inhibitor, with an IC50 of 5 nM for inhibiting the autophosphorylation of p210Bcr-Abl.

In vitro activity:

This study found that PD180970 inhibited in vivo tyrosine phosphorylation of p210Bcr-Abl (IC50 = 170 nM) and the p210BcrAbl substrates Gab2 and CrkL (IC50 = 80 nM) in human K562 chronic myelogenous leukemic cells. In vitro, PD180970 potently inhibited autophosphorylation of p210Bcr-Abl (IC50 = 5 nM) and the kinase activity of purified recombinant Abl tyrosine kinase (IC50 = 2.2 nM). Incubation of K562 cells with PD180970 resulted in cell death. Results of nuclear staining, apoptotic-specific poly(ADP-ribose) polymerase cleavage, and annexin V binding assays indicated that PD180970 induced apoptosis of K562 cells. Reference: Cancer Res. 2000 Jun 15;60(12):3127-31. https://pubmed.ncbi.nlm.nih.gov/10866298/

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	60.0	139.77

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 429.28 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. Huang M, Dorsey JF, Epling-Burnette PK, Nimmanapalli R, Landowski TH, Mora LB, Niu G, Sinibaldi D, Bai F, Kraker A, Yu H, Moscinski L, Wei S, Djeu J, Dalton WS, Bhalla K, Loughran TP, Wu J, Jove R. Inhibition of Bcr-Abl kinase activity by PD180970 blocks constitutive activation of Stat5 and growth of CML cells. Oncogene. 2002 Dec 12;21(57):8804-16. doi: 10.1038/sj.onc.1206028. PMID: 12483533. 2. Dorsey JF, Jove R, Kraker AJ, Wu J. The pyrido[2,3-d]pyrimidine derivative PD180970 inhibits p210Bcr-Abl tyrosine kinase and induces apoptosis of K562 leukemic cells. Cancer Res. 2000 Jun 15;60(12):3127-31. PMID: 10866298.

In vitro protocol:

In vivo protocol:

TBD

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The novel anticancer agent JNJ-26854165 is active in chronic myeloid leukemic cells with unmutated BCR/ABL and T315I mutant BCR/ABL through promoting proteosomal degradation of BCR/ABL proteins. Oncotarget. 2017 Jan 31;8(5):7777-7790. doi: 10.18632/oncotarget.13951. PMID: 27999193; PMCID: PMC5352360. 8: Szafran AT, Stephan C, Bolt M, Mancini MG, Marcelli M, Mancini MA. High- Content Screening Identifies Src Family Kinases as Potential Regulators of AR-V7 Expression and Androgen-Independent Cell Growth. Prostate. 2017 Jan;77(1):82-93. doi: 10.1002/pros.23251. Epub 2016 Oct 4. PMID: 27699828; PMCID: PMC5956900. 9: Wichapong K, Rohe A, Platzer C, Slynko I, Erdmann F, Schmidt M, Sippl W. Application of docking and QM/MM-GBSA rescoring to screen for novel Myt1 kinase inhibitors. J Chem Inf Model. 2014 Mar 24;54(3):881-93. doi: 10.1021/ci4007326. Epub 2014 Feb 13. PMID: 24490903. 10: Geletu M, Guy S, Raptis L. 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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. doi: 10.2174/1389557043487321. PMID: 15032675. 18: Nimmanapalli R, Fuino L, Bali P, Gasparetto M, Glozak M, Tao J, Moscinski L, Smith C, Wu J, Jove R, Atadja P, Bhalla K. Histone deacetylase inhibitor LAQ824 both lowers expression and promotes proteasomal degradation of Bcr-Abl and induces apoptosis of imatinib mesylate-sensitive or -refractory chronic myelogenous leukemia-blast crisis cells. Cancer Res. 2003 Aug 15;63(16):5126-35. PMID: 12941844. 19: Sanguinetti AR, Cao H, Corley Mastick C. Fyn is required for oxidative- and hyperosmotic-stress-induced tyrosine phosphorylation of caveolin-1. Biochem J. 2003 Nov 15;376(Pt 1):159-68. doi: 10.1042/BJ20030336. PMID: 12921535; PMCID: PMC1223754. 20: Song L, Turkson J, Karras JG, Jove R, Haura EB. Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene. 2003 Jul 3;22(27):4150-65. doi: 10.1038/sj.onc.1206479. PMID: 12833138.