TAK-659 HCl | CAS#1312691-41-0 | SYK Inhibitor

MedKoo Cat#: 206169 | Name: TAK-659 HCl

Description:

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

TAK-659 is an inhibitor of spleen tyrosine kinase (syk), with potential anti-inflammatory, immunomodulating, and antineoplastic activities. Spleen tyrosine kinase inhibitor TAK-659 may inhibit the activity of syk, which abrogates downstream B-cell receptor (BCR) signaling and leads to an inhibition of B-cell activation, chemotaxis, adhesion and proliferation. Note: TAK-659 free base is less stable. This product is supplied as dihydrochloride form.

Chemical Structure

TAK-659 HCl

CAS#1312691-41-0 (2HCl)

Theoretical Analysis

MedKoo Cat#: 206169

Name: TAK-659 HCl

CAS#: 1312691-41-0 (2HCl)

Chemical Formula: C17H23Cl2FN6O

Exact Mass: 0.0000

Molecular Weight: 417.31

Elemental Analysis: C, 48.93; H, 5.56; Cl, 16.99; F, 4.55; N, 20.14; O, 3.83

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 850.00	Ready to ship
200mg	USD 1,450.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 3,950.00	Ready to ship
2g	USD 6,950.00	Ready to ship

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Related CAS #

1312691-41-0 (2HCl) 1952251-28-3 (HCl) 1312691-33-0 (free base)

Synonym

TAK659, TAK-659, TAK 659, TAK-659 HCl, TAK659 dihydrochloride

IUPAC/Chemical Name

6-(((1R,2S)-2-aminocyclohexyl)amino)-7-fluoro-4-(1-methyl-1H-pyrazol-4-yl)-1,2-dihydro-3H-pyrrolo[3,4-c]pyridin-3-one dihydrochloride

InChi Key

BZSLKYUVNSVQRA-UVDYRLMLSA-N

InChi Code

InChI=1S/C17H21FN6O.2ClH/c1-24-8-9(6-21-24)15-13-10(7-20-17(13)25)14(18)16(23-15)22-12-5-3-2-4-11(12)19;;/h6,8,11-12H,2-5,7,19H2,1H3,(H,20,25)(H,22,23);2*1H/t11-,12+;;/m0../s1

SMILES Code

O=C1NCC2=C1C(C3=CN(C)N=C3)=NC(N[C@H]4[C@@H](N)CCCC4)=C2F.[H]Cl.[H]Cl

Appearance

White to off-white 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

Certificate of Analysis

View CoA: current batch, Lot#YXM61212

QC Data

View QC data: current batch, Lot#YXM61212

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

N/A

In vitro activity:

To determine whether the pro-survival effect of co-culture and BCR stimulation might be abrogated by TAK-659, this study treated co-cultured and anti-IgM stimulated CLL cells with increasing doses of TAK-659. As displayed in Figure 3A, TAK-659 significantly reduced the viability of CLL cells in a dose-dependent manner, after 48 hours of treatment (mean % viability relative to untreated CLL cells for TAK-659 0.1 μM, 1 μM and 10 μM after 48 hours: 93.51 ± 6.78 vs. 67.91 ± 8.88 vs. 63.05 ± 6.39, respectively, P < 0.001). Reference: Oncotarget. 2017 Jan 3; 8(1): 742–756. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352193/

In vivo activity:

In bone marrow, in both groups of mice that received MYC and LMP2A/MYC primary tumor cells, the percentage of B220-positive tumor cells was significantly decreased with TAK-659 treatment, but this decrease was much more pronounced in the mice with LMP2A/MYC cells (from 47% to 17% in MYC tumor cell recipients and from 60% to less than 10% in LMP2A/MYC tumor recipients) (Fig. 6A, BM graph). Correspondingly, the percentage of CD45.1-positive host cells was increased in the same group of mice (Fig. 6B, left panel). A similar pattern of cellular response was also observed in the spleens and tumors. In the spleens of mice with LMP2A/MYC tumor cells, the percentage of tumor cells was decreased from more than 60% in the buffer-treated mice to a few percent in the TAK-659 treated mice (Fig. 6A). In the same mice, the host cells increased from 25% to more than 80%, respectively (Fig. 6B). In the tumors of mice with both MYC and LMP2A/MYC tumor cells that have been treated with buffer (control group), more than 90% of the cells were B220-positive tumor cells. With TAK-659 treatment, these numbers were decreased to less than 70% and 40%, respectively (Fig. 6A). In the same mice, the percentage of host cells were increased from a few percent in buffer-treated mice to about 10% in mice with MYC tumors and to more than 60% in mice with LMP2A/MYC cells that have been treated with TAK-659, respectively (Fig. 6B). Reference: mSphere. 2018 Jul-Aug; 3(4): e00378-18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106053/

	Solvent	mg/mL	mM
Solubility
	H2O	2.0	5.25

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 417.31 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. Purroy N, Carabia J, Abrisqueta P, Egia L, Aguiló M, Carpio C, Palacio C, Crespo M, Bosch F. Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma-mediated signaling in chronic lymphocytic leukemia cells. Oncotarget. 2017 Jan 3;8(1):742-756. doi: 10.18632/oncotarget.13557. PMID: 27888629; PMCID: PMC5352193. 2. Cen O, Kannan K, Huck Sappal J, Yu J, Zhang M, Arikan M, Ucur A, Ustek D, Cen Y, Gordon L, Longnecker R. Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma. mSphere. 2018 Aug 22;3(4):e00378-18. doi: 10.1128/mSphereDirect.00378-18. PMID: 30135222; PMCID: PMC6106053. 3. Cen O, Kannan K, Huck Sappal J, Yu J, Zhang M, Arikan M, Ucur A, Ustek D, Cen Y, Gordon L, Longnecker R. Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma. mSphere. 2018 Aug 22;3(4):e00378-18. doi: 10.1128/mSphereDirect.00378-18. PMID: 30135222; PMCID: PMC6106053. 4. Lam B, Arikawa Y, Cramlett J, Dong Q, de Jong R, Feher V, Grimshaw CE, Farrell PJ, Hoffman ID, Jennings A, Jones B, Matuszkiewicz J, Miura J, Miyake H, Natala SR, Shi L, Takahashi M, Taylor E, Wyrick C, Yano J, Zalevsky J, Nie Z. Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK). Bioorg Med Chem Lett. 2016 Dec 15;26(24):5947-5950. doi: 10.1016/j.bmcl.2016.10.087. Epub 2016 Nov 2. PMID: 27839918.

In vitro protocol:

In vivo protocol:

1. Cen O, Kannan K, Huck Sappal J, Yu J, Zhang M, Arikan M, Ucur A, Ustek D, Cen Y, Gordon L, Longnecker R. Spleen Tyrosine Kinase Inhibitor TAK-659 Prevents Splenomegaly and Tumor Development in a Murine Model of Epstein-Barr Virus-Associated Lymphoma. mSphere. 2018 Aug 22;3(4):e00378-18. doi: 10.1128/mSphereDirect.00378-18. PMID: 30135222; PMCID: PMC6106053. 2. Lam B, Arikawa Y, Cramlett J, Dong Q, de Jong R, Feher V, Grimshaw CE, Farrell PJ, Hoffman ID, Jennings A, Jones B, Matuszkiewicz J, Miura J, Miyake H, Natala SR, Shi L, Takahashi M, Taylor E, Wyrick C, Yano J, Zalevsky J, Nie Z. Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK). Bioorg Med Chem Lett. 2016 Dec 15;26(24):5947-5950. doi: 10.1016/j.bmcl.2016.10.087. Epub 2016 Nov 2. PMID: 27839918.

1: Purroy N, Carabia J, Abrisqueta P, Egia L, Aguiló M, Carpio C, Palacio C, Crespo M, Bosch F. Inhibition of BCR signaling using the Syk inhibitor TAK-659 prevents stroma-mediated signaling in chronic lymphocytic leukemia cells. Oncotarget. 2016 Nov 24. doi: 10.18632/oncotarget.13557. [Epub ahead of print] PubMed PMID: 27888629. 2: Lam B, Arikawa Y, Cramlett J, Dong Q, de Jong R, Feher V, Grimshaw CE, Farrell PJ, Hoffman ID, Jennings A, Jones B, Matuszkiewicz J, Miura J, Miyake H, Natala SR, Shi L, Takahashi M, Taylor E, Wyrick C, Yano J, Zalevsky J, Nie Z. Discovery of TAK-659 an orally available investigational inhibitor of Spleen Tyrosine Kinase (SYK). Bioorg Med Chem Lett. 2016 Dec 15;26(24):5947-5950. doi: 10.1016/j.bmcl.2016.10.087. PubMed PMID: 27839918. 3. Preparation of fused heteroaromatic pyrrolidinones as SYK inhibitors for treating immune and inflammatory disorders. By Arikawa, Yasuyoshi; Dong, Qing; Feher, Victoria; Jones, Benjamin; Lam, Betty; Nie, Zhe; Smith, Christopher; Takahashi, Masashi. From U.S. Pat. Appl. Publ. (2011), US 20110152273 A1 20110623.