PRT-060318 | PRT-318 | P142–76 | CAS#1194961-19-7 | SYK inhibitor

MedKoo Cat#: 406271 | Name: PRT-060318

Description:

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

PRT-060318, also known as PRT318 or P142–76, is a novel selective inhibitor of the tyrosine kinase Syk, as an approach to HIT treatment. PRT318 completely inhibited HIT immune complex-induced aggregation of both human and transgenic HIT mouse platelets. Transgenic HIT model mice were treated with KKO, a mouse monoclonal HIT-like antibody, and heparin. The experimental group received orally dosed PRT318, whereas the control group received vehicle. Nadir platelet counts of PRT318-treated mice were significantly higher than those of control mice. When examined with a novel thrombosis visualization technique, mice treated with PRT318 had significantly reduced thrombosis.

Chemical Structure

PRT-060318

CAS#1194961-19-7

Theoretical Analysis

MedKoo Cat#: 406271

Name: PRT-060318

CAS#: 1194961-19-7

Chemical Formula: C18H24N6O

Exact Mass: 340.2012

Molecular Weight: 340.42

Elemental Analysis: C, 63.51; H, 7.11; N, 24.69; O, 4.70

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 250.00	2 Weeks
10mg	USD 450.00	2 Weeks

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Related CAS #

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Synonym

PRT060318; PRT 060318; PRT-060318; PRT318; PRT-318; PRT 318; P14-276.

IUPAC/Chemical Name

2-(((1R,2S)-2-aminocyclohexyl)amino)-4-(m-tolylamino)pyrimidine-5-carboxamide

InChi Key

NZNTWOVDIXCHHS-LSDHHAIUSA-N

InChi Code

InChI=1S/C18H24N6O/c1-11-5-4-6-12(9-11)22-17-13(16(20)25)10-21-18(24-17)23-15-8-3-2-7-14(15)19/h4-6,9-10,14-15H,2-3,7-8,19H2,1H3,(H2,20,25)(H2,21,22,23,24)/t14-,15+/m0/s1

SMILES Code

O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(C)=C3)N

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, not soluble in water.

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

More Info

Instruction

View handling instruction

Preparing Stock Solutions

The following data is based on the product molecular weight 340.42 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

1: Zhang P, von Ungern-Sternberg S, Hastenplug L, Solari FA, Sickmann A, Kuijpers MJE, Heemskerk JWM, Walter U, Jurk K. Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation. Thromb Haemost. 2024 May 15. doi: 10.1055/a-2311-0117. Epub ahead of print. PMID: 38653482. 2: Jooss NJ, Henskens YMC, Watson SP, Farndale RW, Gawaz MP, Jandrot-Perrus M, Poulter NS, Heemskerk JWM. Pharmacological Inhibition of Glycoprotein VI- and Integrin α2β1-Induced Thrombus Formation Modulated by the Collagen Type. Thromb Haemost. 2023 Jun;123(6):597-612. doi: 10.1055/s-0043-1761463. Epub 2023 Feb 17. PMID: 36807826. 3: Gauer JS, Duval C, Xu RG, Macrae FL, McPherson HR, Tiede C, Tomlinson D, Watson SP, Ariëns RAS. Fibrin-glycoprotein VI interaction increases platelet procoagulant activity and impacts clot structure. J Thromb Haemost. 2023 Mar;21(3):667-681. doi: 10.1016/j.jtha.2022.09.004. Epub 2022 Dec 22. PMID: 36696196. 4: Kempster C, Butler G, Kuznecova E, Taylor KA, Kriek N, Little G, Sowa MA, Sage T, Johnson LJ, Gibbins JM, Pollitt AY. Fully automated platelet differential interference contrast image analysis via deep learning. Sci Rep. 2022 Mar 17;12(1):4614. doi: 10.1038/s41598-022-08613-2. PMID: 35301400; PMCID: PMC8931011. 5: Perrella G, Montague SJ, Brown HC, Garcia Quintanilla L, Slater A, Stegner D, Thomas M, Heemskerk JWM, Watson SP. Role of Tyrosine Kinase Syk in Thrombus Stabilisation at High Shear. Int J Mol Sci. 2022 Jan 1;23(1):493. doi: 10.3390/ijms23010493. PMID: 35008919; PMCID: PMC8745592. 6: Serafin V, Porcù E, Cortese G, Mariotto E, Veltri G, Bresolin S, Basso G, Accordi B. SYK Targeting Represents a Potential Therapeutic Option for Relapsed Resistant Pediatric ETV6-RUNX1 B-Acute Lymphoblastic Leukemia Patients. Int J Mol Sci. 2019 Dec 7;20(24):6175. doi: 10.3390/ijms20246175. PMID: 31817853; PMCID: PMC6940898. 7: Jooss NJ, De Simone I, Provenzale I, Fernández DI, Brouns SLN, Farndale RW, Henskens YMC, Kuijpers MJE, Ten Cate H, van der Meijden PEJ, Cavill R, Heemskerk JWM. Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces. Int J Mol Sci. 2019 Jun 7;20(11):2788. doi: 10.3390/ijms20112788. PMID: 31181592; PMCID: PMC6600290. 8: Ishikawa C, Senba M, Mori N. Anti-adult T‑cell leukemia/lymphoma activity of cerdulatinib, a dual SYK/JAK kinase inhibitor. Int J Oncol. 2018 Oct;53(4):1681-1690. doi: 10.3892/ijo.2018.4513. Epub 2018 Aug 1. PMID: 30066853. 9: Badolia R, Kostyak JC, Dangelmaier C, Kunapuli SP. Syk Activity Is Dispensable for Platelet GP1b-IX-V Signaling. Int J Mol Sci. 2017 Jun 9;18(6):1238. doi: 10.3390/ijms18061238. PMID: 28598382; PMCID: PMC5486061. 10: Nanì S, Fumagalli L, Sinha U, Kamen L, Scapini P, Berton G. Src family kinases and Syk are required for neutrophil extracellular trap formation in response to β-glucan particles. J Innate Immun. 2015;7(1):59-73. doi: 10.1159/000365249. Epub 2014 Sep 24. PMID: 25277753; PMCID: PMC6951106. 11: Cheng S, Guo A, Lu P, Ma J, Coleman M, Wang YL. Functional characterization of BTK(C481S) mutation that confers ibrutinib resistance: exploration of alternative kinase inhibitors. Leukemia. 2015 Apr;29(4):895-900. doi: 10.1038/leu.2014.263. Epub 2014 Sep 5. PMID: 25189416. 12: Hoellenriegel J, Coffey GP, Sinha U, Pandey A, Sivina M, Ferrajoli A, Ravandi F, Wierda WG, O'Brien S, Keating MJ, Burger JA. Selective, novel spleen tyrosine kinase (Syk) inhibitors suppress chronic lymphocytic leukemia B-cell activation and migration. Leukemia. 2012 Jul;26(7):1576-83. doi: 10.1038/leu.2012.24. Epub 2012 Feb 7. PMID: 22362000; PMCID: PMC5459370. 13: Andre P, Morooka T, Sim D, Abe K, Lowell C, Nanda N, Delaney S, Siu G, Yan Y, Hollenbach S, Pandey A, Gao H, Wang Y, Nakajima K, Parikh SA, Shi C, Phillips D, Owen W, Sinha U, Simon DI. Critical role for Syk in responses to vascular injury. Blood. 2011 Nov 3;118(18):5000-10. doi: 10.1182/blood-2011-06-360743. Epub 2011 Aug 31. PMID: 21881044; PMCID: PMC3208305. 14: Reilly MP, Sinha U, André P, Taylor SM, Pak Y, Deguzman FR, Nanda N, Pandey A, Stolla M, Bergmeier W, McKenzie SE. PRT-060318, a novel Syk inhibitor, prevents heparin-induced thrombocytopenia and thrombosis in a transgenic mouse model. Blood. 2011 Feb 17;117(7):2241-6. doi: 10.1182/blood-2010-03-274969. Epub 2010 Nov 18. PMID: 21088136; PMCID: PMC3568699.