IUPAC/Chemical Name
1-(tert-butyl)-3-(p-tolyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
InChi Key
ZVPDNRVYHLRXLX-UHFFFAOYSA-N
InChi Code
InChI=1S/C16H19N5/c1-10-5-7-11(8-6-10)13-12-14(17)18-9-19-15(12)21(20-13)16(2,3)4/h5-9H,1-4H3,(H2,17,18,19)
SMILES Code
NC1=C2C(N(C(C)(C)C)N=C2C3=CC=C(C)C=C3)=NC=N1
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
>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
2934.99.9001
Biological target:
PP1 is a potent, and Src family-selective tyrosine kinase inhibitor with IC50 of 5 and 6 nM for Lck and Fyn.
In vitro activity:
PP1 inhibited SCF-induced c-Kit autophosphorylation in intact cells and blocked the activation of mitogen-activated protein kinase and Akt. In vitro kinase assays using immunoprecipitated c-Kit confirmed direct inhibition by PP1. SCF-induced c-Kit phosphorylation was also inhibited by the related inhibitor 4-amino-5- (4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]-pyrimidine (PP2) and by STI571 but not by the Src inhibitor SU6656. PP1 inhibited the activity of mutant constitutively active forms of c-Kit (D814V and D814Y) found in mast cell disorders, and triggered apoptosis in the rat basophilic leukemia cell line RBL-2H3 that expresses mutant c-Kit. In addition, PP1 (and PP2) inhibited the in vitro kinase activity and autophosphorylation in whole cells of p210 Bcr-Abl. PP1 reduced the constitutive activation of signal transducer and activators of transcription 5 and mitogen-activated protein kinase and triggered apoptosis in FDCP1 cells expressing Bcr-Abl.
Reference: J Biol Chem. 2003 Feb 14;278(7):4847-53. https://pubmed.ncbi.nlm.nih.gov/12475982/
In vivo activity:
PP1 prevented the growth of two human papillary thyroid carcinoma cell lines that carry spontaneous RET/PTC1 rearrangements and blocked anchorage-independent growth and tumorigenicity in nude mice of NIH3T3 fibroblasts expressing the RET/PTC3 oncogene. These findings suggest targeting RET oncogenes with PP1 or related compounds as a novel treatment strategy for RET-associated neoplasms.
Reference: Cancer Res. 2002 Feb 15;62(4):1077-82. https://pubmed.ncbi.nlm.nih.gov/11861385/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
3.0 |
10.66 |
| DMF:PBS (pH 7.2) (1:9) |
0.1 |
0.36 |
| DMSO |
11.3 |
40.28 |
| Ethanol |
0.2 |
0.53 |
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
281.36
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. Tatton L, Morley GM, Chopra R, Khwaja A. The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases. J Biol Chem. 2003 Feb 14;278(7):4847-53. doi: 10.1074/jbc.M209321200. Epub 2002 Dec 9. PMID: 12475982.
2. Liu Y, Bishop A, Witucki L, Kraybill B, Shimizu E, Tsien J, Ubersax J, Blethrow J, Morgan DO, Shokat KM. Structural basis for selective inhibition of Src family kinases by PP1. Chem Biol. 1999 Sep;6(9):671-8. doi: 10.1016/s1074-5521(99)80118-5. PMID: 10467133.
3. Turel MK, Moorthy RK, Sam GA, Samuel P, Murthy M, Babu KS, Rajshekhar V. Effect of pretreatment with a tyrosine kinase inhibitor (PP1) on brain oedema and neurological function in an automated cortical cryoinjury model in mice. J Clin Neurosci. 2013 Apr;20(4):593-6. doi: 10.1016/j.jocn.2012.06.009. Epub 2013 Feb 26. PMID: 23485404.
4. Carlomagno F, Vitagliano D, Guida T, Napolitano M, Vecchio G, Fusco A, Gazit A, Levitzki A, Santoro M. The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Res. 2002 Feb 15;62(4):1077-82. PMID: 11861385.
In vitro protocol:
1. Tatton L, Morley GM, Chopra R, Khwaja A. The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases. J Biol Chem. 2003 Feb 14;278(7):4847-53. doi: 10.1074/jbc.M209321200. Epub 2002 Dec 9. PMID: 12475982.
2. Liu Y, Bishop A, Witucki L, Kraybill B, Shimizu E, Tsien J, Ubersax J, Blethrow J, Morgan DO, Shokat KM. Structural basis for selective inhibition of Src family kinases by PP1. Chem Biol. 1999 Sep;6(9):671-8. doi: 10.1016/s1074-5521(99)80118-5. PMID: 10467133.
In vivo protocol:
1. Turel MK, Moorthy RK, Sam GA, Samuel P, Murthy M, Babu KS, Rajshekhar V. Effect of pretreatment with a tyrosine kinase inhibitor (PP1) on brain oedema and neurological function in an automated cortical cryoinjury model in mice. J Clin Neurosci. 2013 Apr;20(4):593-6. doi: 10.1016/j.jocn.2012.06.009. Epub 2013 Feb 26. PMID: 23485404.
2. Carlomagno F, Vitagliano D, Guida T, Napolitano M, Vecchio G, Fusco A, Gazit A, Levitzki A, Santoro M. The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Res. 2002 Feb 15;62(4):1077-82. PMID: 11861385.
1: Turel MK, Moorthy RK, Sam GA, Samuel P, Murthy M, Babu KS, Rajshekhar V. Effect of pretreatment with a tyrosine kinase inhibitor (PP1) on brain oedema and neurological function in an automated cortical cryoinjury model in mice. J Clin Neurosci. 2013 Apr;20(4):593-6. doi: 10.1016/j.jocn.2012.06.009. Epub 2013 Feb 26. PubMed PMID: 23485404.
2: Bartscht T, Lehnert H, Gieseler F, Ungefroren H. The Src family kinase inhibitors PP2 and PP1 effectively block TGF-beta1-induced cell migration and invasion in both established and primary carcinoma cells. Cancer Chemother Pharmacol. 2012 Aug;70(2):221-30. doi: 10.1007/s00280-012-1904-0. Epub 2012 Jun 15. PubMed PMID: 22699812.
3: Ungefroren H, Sebens S, Groth S, Gieseler F, Fändrich F. The Src family kinase inhibitors PP2 and PP1 block TGF-beta1-mediated cellular responses by direct and differential inhibition of type I and type II TGF-beta receptors. Curr Cancer Drug Targets. 2011 May;11(4):524-35. PubMed PMID: 21395548.
4: Maeda M, Shintani Y, Wheelock MJ, Johnson KR. Src activation is not necessary for transforming growth factor (TGF)-beta-mediated epithelial to mesenchymal transitions (EMT) in mammary epithelial cells. PP1 directly inhibits TGF-beta receptors I and II. J Biol Chem. 2006 Jan 6;281(1):59-68. Epub 2005 Nov 1. PubMed PMID: 16267045.
5: Dickerson J, Sharp FR. Atypical antipsychotics and a Src kinase inhibitor (PP1) prevent cortical injury produced by the psychomimetic, noncompetitive NMDA receptor antagonist MK-801. Neuropsychopharmacology. 2006 Jul;31(7):1420-30. Epub 2005 Aug 17. PubMed PMID: 16123741.
6: Fujimoto E, Sato H, Nagashima Y, Negishi E, Shirai S, Fukumoto K, Hagiwara H, Hagiwara K, Ueno K, Yano T. A Src family inhibitor (PP1) potentiates tumor-suppressive effect of connexin 32 gene in renal cancer cells. Life Sci. 2005 Apr 22;76(23):2711-20. Epub 2005 Jan 28. PubMed PMID: 15792837.
7: Akiyama C, Yuguchi T, Nishio M, Tomishima T, Fujinaka T, Taniguchi M, Nakajima Y, Kohmura E, Yoshimine T. Src family kinase inhibitor PP1 reduces secondary damage after spinal cord compression in rats. J Neurotrauma. 2004 Jul;21(7):923-31. PubMed PMID: 15307904.
