PD166326 | CAS#185039-91-2 | protein tyrosine kinase inhibitor

MedKoo Cat#: 406173 | Name: PD166326

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Description:

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

PD166326 is one of the most potent members of the pyridopyrimidine class of protein tyrosine kinase inhibitors. In mice with the CML-like disease, PD166326 rapidly inhibited Bcr/Abl kinase activity after a single oral dose and demonstrated marked antileukemic activity in vivo. In vivo, PD166326 was also superior to imatinib mesylate in inhibiting the constitutive tyrosine phosphorylation of numerous leukemia-cell proteins, including the src family member Lyn. PD166326 also prolonged the survival of mice with imatinib mesylate-resistant CML induced by the Bcr/Abl mutants P210/H396P and P210/M351T.

Chemical Structure

PD166326

CAS#185039-91-2

Theoretical Analysis

MedKoo Cat#: 406173

Name: PD166326

CAS#: 185039-91-2

Chemical Formula: C21H16Cl2N4O2

Exact Mass: 426.0650

Molecular Weight: 427.28

Elemental Analysis: C, 59.03; H, 3.77; Cl, 16.59; N, 13.11; O, 7.49

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 450.00	2 Weeks
25mg	USD 900.00	2 Weeks

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Related CAS #

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Synonym

PD166326; PD166326; PD 166326.

IUPAC/Chemical Name

6-(2,6-dichlorophenyl)-2-((3-(hydroxymethyl)phenyl)amino)-8-methylpyrido[2,3-d]pyrimidin-7(8H)-one

InChi Key

ZIQFYVPVJZEOFS-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H16Cl2N4O2/c1-27-19-13(9-15(20(27)29)18-16(22)6-3-7-17(18)23)10-24-21(26-19)25-14-5-2-4-12(8-14)11-28/h2-10,28H,11H2,1H3,(H,24,25,26)

SMILES Code

O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3=CN=C(NC4=CC=CC(CO)=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:

PD166326 is a pyridopyrimidine-type inhibitor of receptor tyrosine kinases, with IC50s of 6 nM and 8 nM for Src and Abl.

In vitro activity:

PD166326 potently inhibits the E255K mutant Bcr-abl protein and the growth of Bcr-ablE255K-driven cells. The T315I mutant Bcr-abl protein, which is mutated within the ATP-binding pocket, is resistant to PD166326; however, the growth of Bcr-ablT315I-driven cells is partially sensitive to this compound, likely through the inhibition of Bcr-abl effector pathways. These findings show that TK drug resistance is a structure-specific phenomenon and can be overcome by TK inhibitors of other structural classes, suggesting new approaches for future anticancer drug development. Reference: Clin Cancer Res. 2003 Apr;9(4):1267-73. https://pubmed.ncbi.nlm.nih.gov/12684394/

In vivo activity:

In mice with the CML-like disease, PD166326 rapidly inhibited Bcr/Abl kinase activity after a single oral dose and demonstrated marked antileukemic activity in vivo. Seventy percent of PD166326-treated mice achieved a white blood cell (WBC) count less than 20.0 x 10(9)/L (20,000/microL) at necropsy, compared with only 8% of imatinib mesylate-treated animals. Further, two thirds of PD166326-treated animals had complete resolution of splenomegaly, compared with none of the imatinib mesylate-treated animals. Reference: Blood. 2005 May 15;105(10):3995-4003. https://pubmed.ncbi.nlm.nih.gov/15657179/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	70.21
	DMSO:PBS (pH 7.2) (1:4)	0.2	0.47
	DMSO	62.5	146.27

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 427.28 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. Huron DR, Gorre ME, Kraker AJ, Sawyers CL, Rosen N, Moasser MM. A novel pyridopyrimidine inhibitor of abl kinase is a picomolar inhibitor of Bcr-abl-driven K562 cells and is effective against STI571-resistant Bcr-abl mutants. Clin Cancer Res. 2003 Apr;9(4):1267-73. PMID: 12684394. 2. Wisniewski D, Lambek CL, Liu C, Strife A, Veach DR, Nagar B, Young MA, Schindler T, Bornmann WG, Bertino JR, Kuriyan J, Clarkson B. Characterization of potent inhibitors of the Bcr-Abl and the c-kit receptor tyrosine kinases. Cancer Res. 2002 Aug 1;62(15):4244-55. PMID: 12154026. 3. Wolff NC, Veach DR, Tong WP, Bornmann WG, Clarkson B, Ilaria RL Jr. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood. 2005 May 15;105(10):3995-4003. doi: 10.1182/blood-2004-09-3534. Epub 2005 Jan 18. PMID: 15657179; PMCID: PMC1895078.

In vitro protocol:

In vivo protocol:

1. Wolff NC, Veach DR, Tong WP, Bornmann WG, Clarkson B, Ilaria RL Jr. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood. 2005 May 15;105(10):3995-4003. doi: 10.1182/blood-2004-09-3534. Epub 2005 Jan 18. PMID: 15657179; PMCID: PMC1895078.

1: Grosso S, Puissant A, Dufies M, Colosetti P, Jacquel A, Lebrigand K, Barbry P, Deckert M, Cassuto JP, Mari B, Auberger P. Gene expression profiling of imatinib and PD166326-resistant CML cell lines identifies Fyn as a gene associated with resistance to BCR-ABL inhibitors. Mol Cancer Ther. 2009 Jul;8(7):1924-33. doi: 10.1158/1535-7163.MCT-09-0168. Epub 2009 Jun 30. PubMed PMID: 19567819. 2: Wolff NC, Veach DR, Tong WP, Bornmann WG, Clarkson B, Ilaria RL Jr. PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia. Blood. 2005 May 15;105(10):3995-4003. Epub 2005 Jan 18. PubMed PMID: 15657179; PubMed Central PMCID: PMC1895078. 3: von Bubnoff N, Veach DR, van der Kuip H, Aulitzky WE, SÃ¤nger J, Seipel P, Bornmann WG, Peschel C, Clarkson B, Duyster J. A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor. Blood. 2005 Feb 15;105(4):1652-9. Epub 2004 Sep 30. PubMed PMID: 15459011.