PRT062607 HCl | CAS#1370261-97-4 | SYK inhibitor

MedKoo Cat#: 406272 | Name: PRT062607 HCl

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Description:

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

PRT062607 (also known as P505-15, PRT2607, PRT62607, and BIIB057) is a highly selective, and orally bioavailable small molecule SYK inhibitor.

Chemical Structure

PRT062607 HCl

CAS#1370261-97-4 (HCl)

Theoretical Analysis

MedKoo Cat#: 406272

Name: PRT062607 HCl

CAS#: 1370261-97-4 (HCl)

Chemical Formula: C19H24ClN9O

Exact Mass: 393.2026

Molecular Weight: 429.91

Elemental Analysis: C, 53.08; H, 5.63; Cl, 8.25; N, 29.32; O, 3.72

Price and Availability

Size	Price	Availability
50mg	USD 550.00	2 Weeks
100mg	USD 950.00	2 Weeks
200mg	USD 1,550.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,650.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

1370261-97-4 (HCl) 1370261-96-3 (free base)

Synonym

PRT2607; PRT-2607; PRT 2607; PRT062607; PRT-062607; PRT 062607; BIIB057; BIIB-057; BIIB 057; P-505-15; P 505-15; P505-15; P-50515; P 50515; P50515

IUPAC/Chemical Name

4-((3-(2H-1,2,3-triazol-2-yl)phenyl)amino)-2-(((1R,2S)-2-aminocyclohexyl)amino)pyrimidine-5-carboxamide hydrochloride

InChi Key

RMNLLPXCNDZJMJ-IDVLALEDSA-N

InChi Code

InChI=1S/C19H23N9O.ClH/c20-15-6-1-2-7-16(15)26-19-22-11-14(17(21)29)18(27-19)25-12-4-3-5-13(10-12)28-23-8-9-24-28;/h3-5,8-11,15-16H,1-2,6-7,20H2,(H2,21,29)(H2,22,25,26,27);1H/t15-,16+;/m0./s1

SMILES Code

O=C(C1=CN=C(N[C@H]2[C@@H](N)CCCC2)N=C1NC3=CC=CC(N4N=CC=N4)=C3)N.[H]Cl

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

To be determined

Shelf Life

>2 years if stored properly

Drug Formulation

To be determined

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:

PRT062607 HCl is a SYK inhibitor with an IC50 value of 1-2 nM.

In vitro activity:

PRT062607 exhibited inhibitory effects on osteoclast-specific gene expression, bone resorption, and osteoclastogenesis induced by RANKL. PRT062607 demonstrated suppressive effects on the growth, migration, and invasion of MDA-MB-231 cells. These actions were attributed to its influence on PLCγ2 and the PI3K-AKT-mTOR pathways. PRT062607 shows potential for managing osteolytic diseases associated with osteoclasts. Reference: Biochem Pharmacol. 2021 Jun;188:114579. https://pubmed.ncbi.nlm.nih.gov/33895161/

In vivo activity:

PRT062607 exhibited a favorable pharmacokinetic profile and effectively inhibited SYK activity in whole-blood assay. The compound demonstrated selectivity for SYK at all tested dose levels. Analysis of the pharmacokinetic/pharmacodynamic relationship revealed its potential in inhibiting B-cell antigen receptor-mediated B-cell activation and FcεRI-mediated basophil degranulation, with IC50 values of 324 nM and 205 nM, respectively. PRT062607 exhibited anti-inflammatory activity in a rat model. Reference: J Clin Pharmacol. 2017 Feb;57(2):194-210. https://pubmed.ncbi.nlm.nih.gov/27406873/

Preparing Stock Solutions

The following data is based on the product molecular weight 429.91 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. Xie G, Liu W, Lian Z, Xie D, Yuan G, Ye J, Lin Z, Wang W, Zeng J, Shen H, Wang X, Feng H, Cong W, Yao G. Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction. Biochem Pharmacol. 2021 Jun;188:114579. doi: 10.1016/j.bcp.2021.114579. Epub 2021 Apr 23. PMID: 33895161. 2. 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. 3. Coffey G, Rani A, Betz A, Pak Y, Haberstock-Debic H, Pandey A, Hollenbach S, Gretler DD, Mant T, Jurcevic S, Sinha U. PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers. J Clin Pharmacol. 2017 Feb;57(2):194-210. doi: 10.1002/jcph.794. Epub 2016 Aug 17. PMID: 27406873; PMCID: PMC5248591. 4. Spurgeon SE, Coffey G, Fletcher LB, Burke R, Tyner JW, Druker BJ, Betz A, DeGuzman F, Pak Y, Baker D, Pandey A, Hollenbach SJ, Sinha U, Loriaux MM. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia. J Pharmacol Exp Ther. 2013 Feb;344(2):378-87. doi: 10.1124/jpet.112.200832. Epub 2012 Dec 7. PMID: 23220742; PMCID: PMC3558816.

In vitro protocol:

In vivo protocol:

1. Coffey G, Rani A, Betz A, Pak Y, Haberstock-Debic H, Pandey A, Hollenbach S, Gretler DD, Mant T, Jurcevic S, Sinha U. PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers. J Clin Pharmacol. 2017 Feb;57(2):194-210. doi: 10.1002/jcph.794. Epub 2016 Aug 17. PMID: 27406873; PMCID: PMC5248591. 2. Spurgeon SE, Coffey G, Fletcher LB, Burke R, Tyner JW, Druker BJ, Betz A, DeGuzman F, Pak Y, Baker D, Pandey A, Hollenbach SJ, Sinha U, Loriaux MM. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia. J Pharmacol Exp Ther. 2013 Feb;344(2):378-87. doi: 10.1124/jpet.112.200832. Epub 2012 Dec 7. PMID: 23220742; PMCID: PMC3558816.

1: Rasool S, Shomali T, Truong L, Croteau N, Veyron S, Bustillos BA, Springer W, Fiesel FC, Trempe JF. Identification and structural characterization of small molecule inhibitors of PINK1. Sci Rep. 2024 Apr 2;14(1):7739. doi: 10.1038/s41598-024-58285-3. PMID: 38565869; PMCID: PMC10987619. 2: Tang S, Yu Q, Ding C. Investigational spleen tyrosine kinase (SYK) inhibitors for the treatment of autoimmune diseases. Expert Opin Investig Drugs. 2022 Mar;31(3):291-303. doi: 10.1080/13543784.2022.2040014. Epub 2022 Feb 18. PMID: 35130124. 3: Xie G, Liu W, Lian Z, Xie D, Yuan G, Ye J, Lin Z, Wang W, Zeng J, Shen H, Wang X, Feng H, Cong W, Yao G. Spleen tyrosine kinase (SYK) inhibitor PRT062607 protects against ovariectomy-induced bone loss and breast cancer-induced bone destruction. Biochem Pharmacol. 2021 Jun;188:114579. doi: 10.1016/j.bcp.2021.114579. Epub 2021 Apr 23. PMID: 33895161. 4: Torres-Hernandez A, Wang W, Nikiforov Y, Tejada K, Torres L, Kalabin A, Wu Y, Haq MIU, Khan MY, Zhao Z, Su W, Camargo J, Hundeyin M, Diskin B, Adam S, Rossi JAK, Kurz E, Aykut B, Shadaloey SAA, Leinwand J, Miller G. Targeting SYK signaling in myeloid cells protects against liver fibrosis and hepatocarcinogenesis. Oncogene. 2019 Jun;38(23):4512-4526. doi: 10.1038/s41388-019-0734-5. Epub 2019 Feb 11. PMID: 30742098. 5: Coffey G, Rani A, Betz A, Pak Y, Haberstock-Debic H, Pandey A, Hollenbach S, Gretler DD, Mant T, Jurcevic S, Sinha U. PRT062607 Achieves Complete Inhibition of the Spleen Tyrosine Kinase at Tolerated Exposures Following Oral Dosing in Healthy Volunteers. J Clin Pharmacol. 2017 Feb;57(2):194-210. doi: 10.1002/jcph.794. Epub 2016 Aug 17. PMID: 27406873; PMCID: PMC5248591. 6: Llop-Guevara A, Porras M, Cendón C, Di Ceglie I, Siracusa F, Madarena F, Rinotas V, Gómez L, van Lent PL, Douni E, Chang HD, Kamradt T, Román J. Simultaneous inhibition of JAK and SYK kinases ameliorates chronic and destructive arthritis in mice. Arthritis Res Ther. 2015 Dec 10;17:356. doi: 10.1186/s13075-015-0866-0. PMID: 26653844; PMCID: PMC4675041. 7: Parente-Ribes A, Skånland SS, Bürgler S, Os A, Wang D, Bogen B, Tjønnfjord GE, Taskén K, Munthe LA. Spleen tyrosine kinase inhibitors reduce CD40L-induced proliferation of chronic lymphocytic leukemia cells but not normal B cells. Haematologica. 2016 Feb;101(2):e59-62. doi: 10.3324/haematol.2015.135590. Epub 2015 Nov 20. PMID: 26589914; PMCID: PMC4938324. 8: Zhang Z, Cao C, Sun S, Xu Q. Selective spleen tyrosine kinase inhibition delays autoimmune arthritis in mice. Mol Med Rep. 2015 Aug;12(2):2902-6. doi: 10.3892/mmr.2015.3759. Epub 2015 May 8. PMID: 25955571. 9: Coffey G, Betz A, Graf J, Stephens G, Hua Lin P, Imboden J, Sinha U. Methotrexate and a spleen tyrosine kinase inhibitor cooperate to inhibit responses to peripheral blood B cells in rheumatoid arthritis. Pharmacol Res Perspect. 2013 Dec;1(2):e00016. doi: 10.1002/prp2.16. Epub 2013 Dec 15. PMID: 25505569; PMCID: PMC4186432. 10: Spurgeon SE, Coffey G, Fletcher LB, Burke R, Tyner JW, Druker BJ, Betz A, DeGuzman F, Pak Y, Baker D, Pandey A, Hollenbach SJ, Sinha U, Loriaux MM. The selective SYK inhibitor P505-15 (PRT062607) inhibits B cell signaling and function in vitro and in vivo and augments the activity of fludarabine in chronic lymphocytic leukemia. J Pharmacol Exp Ther. 2013 Feb;344(2):378-87. doi: 10.1124/jpet.112.200832. Epub 2012 Dec 7. PMID: 23220742; PMCID: PMC3558816. 11: 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. 12: Coffey G, DeGuzman F, Inagaki M, Pak Y, Delaney SM, Ives D, Betz A, Jia ZJ, Pandey A, Baker D, Hollenbach SJ, Phillips DR, Sinha U. Specific inhibition of spleen tyrosine kinase suppresses leukocyte immune function and inflammation in animal models of rheumatoid arthritis. J Pharmacol Exp Ther. 2012 Feb;340(2):350-9. doi: 10.1124/jpet.111.188441. Epub 2011 Oct 31. PMID: 22040680.