Takinib | CAS#1111556-37-6 | TAK1 inhibitor

MedKoo Cat#: 561836 | Name: Takinib

Description:

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

Takinib is a selective TAK1 inhibitor that induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer. Takinib is an inhibitor of autophosphorylated and non-phosphorylated TAK1 that binds within the ATP-binding pocket and inhibits by slowing down the rate-limiting step of TAK1 activation.

Chemical Structure

Takinib

CAS#1111556-37-6

Theoretical Analysis

MedKoo Cat#: 561836

Name: Takinib

CAS#: 1111556-37-6

Chemical Formula: C18H18N4O2

Exact Mass: 322.1430

Molecular Weight: 322.36

Elemental Analysis: C, 67.07; H, 5.63; N, 17.38; O, 9.93

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 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 1,950.00	Ready to ship
1g	USD 2,950.00	Ready to ship
2g	USD 5,250.00	Ready to ship

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Related CAS #

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Synonym

Takinib; EDHS-206; EDHS 206; EDHS206;

IUPAC/Chemical Name

3-N-(1-Propylbenzimidazol-2-yl)benzene-1,3-dicarboxamide

InChi Key

UOZVVPXKJGOFIG-UHFFFAOYSA-N

InChi Code

InChI=1S/C18H18N4O2/c1-2-10-22-15-9-4-3-8-14(15)20-18(22)21-17(24)13-7-5-6-12(11-13)16(19)23/h3-9,11H,2,10H2,1H3,(H2,19,23)(H,20,21,24)

SMILES Code

O=C(C1=CC=CC(C(NC2=NC3=CC=CC=C3N2CCC)=O)=C1)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

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#B8B06C09

QC Data

View QC data: current batch, Lot#B8B06C09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Takinib is a potent and selective TAK1 inhibitor with an IC50 of 9.5 nM.

In vitro activity:

MDA-MB-231 cells were serum-starved for 3h and pre-treated with 10μM Takinib for 2h. Stimulation of cells with TNFα was performed over a time-course of 60min and the phosphorylation status of IKK, p38, and p65 was determined via Western Blot (Fig. 5B). IKK and p65 are maximally phosphorylated at 15 minutes, which indicate activation of the NFkB pathway, while p38 phosphorylation peaks at 30 minutes. Takinib reduced phosphorylation of significantly but did not influence total protein levels. Dose-dependency studies were performed in Hela cells following 15 minutes of TNFα stimulation. Western Blot analysis demonstrated that Takinib inhibits phosphorylation of IKK, MAPK 8/9, and cJun in a dose-dependent manner (Fig. 5C). Additionally, we investigated cellular TAK1 autophosphorylation following 15min of TNFα stimulation. Thr184 phosphorylation was significantly reduced at low μM concentrations (Fig. S3A). Reference: Cell Chem Biol. 2017 Aug 17;24(8):1029-1039.e7. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/28820959/

In vivo activity:

Takinib has an ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. Reference: Arthritis Res Ther. 2019 Dec 17;21(1):292. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/31847895/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	93.06

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 322.36 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:

In vitro protocol:

1. Totzke J, Gurbani D, Raphemot R, Hughes PF, Bodoor K, Carlson DA, Loiselle DR, Bera AK, Eibschutz LS, Perkins MM, Eubanks AL, Campbell PL, Fox DA, Westover KD, Haystead TAJ, Derbyshire ER. Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease. Cell Chem Biol. 2017 Aug 17;24(8):1029-1039.e7. doi: 10.1016/j.chembiol.2017.07.011. PMID: 28820959; PMCID: PMC5576570.

In vivo protocol:

1. Scarneo SA, Eibschutz LS, Bendele PJ, Yang KW, Totzke J, Hughes P, Fox DA, Haystead TAJ. Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice. Arthritis Res Ther. 2019 Dec 17;21(1):292. doi: 10.1186/s13075-019-2073-x. PMID: 31847895; PMCID: PMC6918687.

1: Banisharif Dehkordi F, Ghatrehsamani M, Abdolvand M, Soltani A, Masoumi SH. Impact of Combination Therapy with Chemical Drugs and Megavoltage X-ray Exposure on Breast Cancer Stem Cells' Viability and Proliferation of MCF-7 and MDA-MB-231 Cell Lines. Curr Pharm Des. 2024;30(17):1341-1353. doi: 10.2174/0113816128287325240329085055. PMID: 38676476. 2: Hao S, Yuan S, Liu Z, Hou B, Feng S, Zhang D. Neuroprotective effects of takinib on an experimental traumatic brain injury rat model via inhibition of transforming growth factor beta-activated kinase 1. Heliyon. 2024 Apr 10;10(8):e29484. doi: 10.1016/j.heliyon.2024.e29484. PMID: 38644820; PMCID: PMC11033159. 3: Akwata D, Kempen AL, Lamptey J, Dayal N, Brauer NR, Sintim HO. Discovery of imidazo[1,2-b]pyridazine-containing TAK1 kinase inhibitors with excellent activities against multiple myeloma. RSC Med Chem. 2023 Nov 28;15(1):178-192. doi: 10.1039/d3md00415e. PMID: 38283221; PMCID: PMC10809330. 4: Guo X, Liu M, Han B, Zheng Y, Zhang K, Bao G, Gao C, Shi H, Sun Q, Zhao Z. Upregulation of TRIM16 mitigates doxorubicin-induced cardiotoxicity by modulating TAK1 and YAP/Nrf2 pathways in mice. Biochem Pharmacol. 2024 Feb;220:116009. doi: 10.1016/j.bcp.2023.116009. Epub 2023 Dec 26. PMID: 38154547. 5: Wang W, Pang C, Zhang J, Peng L, Zhang X, Shi L, Zhang H. Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway. Front Immunol. 2023 Nov 14;14:1266315. doi: 10.3389/fimmu.2023.1266315. PMID: 38035075; PMCID: PMC10682771. 6: Abdolvand M, Shahini Shams Abadi M, Soltani A, Banisharif F, Ghatrehsamani M. Chronic treatment with TNF-α, alone and in combination with Takinib, SB203580 and metformin induce cell death in breast cancer. Heliyon. 2023 Oct 16;9(11):e21060. doi: 10.1016/j.heliyon.2023.e21060. PMID: 37964831; PMCID: PMC10641119. 7: Zhang Y, Su Y, Wang Z, Li T, Wang L, Ma D, Zhou M. TAK1 Reduces Surgery- induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats. Neurochem Res. 2023 Oct;48(10):3073-3083. doi: 10.1007/s11064-023-03959-z. Epub 2023 Jun 17. PMID: 37329446; PMCID: PMC10471686. 8: Scarneo S, Zhang X, Wang Y, Camacho-Domenech J, Ricano J, Hughes P, Haystead T, Nackley AG. Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain. J Pain. 2023 Sep;24(9):1633-1644. doi: 10.1016/j.jpain.2023.04.011. Epub 2023 Apr 29. PMID: 37121498; PMCID: PMC10524186. 9: Scarneo S, Hughes P, Freeze R, Yang K, Totzke J, Haystead T. Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis. ACS Chem Biol. 2022 Mar 18;17(3):536-544. doi: 10.1021/acschembio.1c00788. Epub 2022 Mar 2. PMID: 35234444; PMCID: PMC9245008. 10: Panipinto PM, Singh AK, Shaikh FS, Siegel RJ, Chourasia M, Ahmed S. Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway. Int J Mol Sci. 2021 Nov 22;22(22):12580. doi: 10.3390/ijms222212580. PMID: 34830460; PMCID: PMC8621335. 11: Pietri JE, Potts R. Effects of NF-kB Signaling Inhibitors on Bed Bug Resistance to Orally Provisioned Entomopathogenic Bacteria. Insects. 2021 Mar 30;12(4):303. doi: 10.3390/insects12040303. PMID: 33808065; PMCID: PMC8067208. 12: Song Z, Wei W, Xiao W, Al-Saleem ED, Nejati R, Chen L, Yin J, Fabrizio J, Petrus MN, Waldmann TA, Yang Y. Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma. Proc Natl Acad Sci U S A. 2020 Nov 17;117(46):28980-28991. doi: 10.1073/pnas.2014470117. Epub 2020 Nov 2. PMID: 33139544; PMCID: PMC7682429. 13: Da Q, Yan Z, Li Z, Han Z, Ren M, Huang L, Zhang X, Liu J, Wang T. TAK1 is involved in sodium L-lactate-stimulated p38 signaling and promotes apoptosis. Mol Cell Biochem. 2021 Feb;476(2):873-882. doi: 10.1007/s11010-020-03952-y. Epub 2020 Oct 27. Erratum in: Mol Cell Biochem. 2021 Jul;476(7):2889-2890. doi: 10.1007/s11010-021-04184-4. PMID: 33111211. 14: Scarneo SA, Yang KW, Roques JR, Dai A, Eibschutz LS, Hughes P, Haystead TAJ. TAK1 regulates the tumor microenvironment through inflammatory, angiogenetic and apoptotic signaling cascades. Oncotarget. 2020 May 26;11(21):1961-1970. doi: 10.18632/oncotarget.27606. PMID: 32523651; PMCID: PMC7260121. 15: Scarneo SA, Hughes PF, Yang KW, Carlson DA, Gurbani D, Westover KD, Haystead TAJ. A highly selective inhibitor of interleukin-1 receptor-associated kinases 1/4 (IRAK-1/4) delineates the distinct signaling roles of IRAK-1/4 and the TAK1 kinase. J Biol Chem. 2020 Feb 7;295(6):1565-1574. doi: 10.1074/jbc.RA119.011857. Epub 2019 Dec 30. PMID: 31914413; PMCID: PMC7008364. 16: Scarneo SA, Eibschutz LS, Bendele PJ, Yang KW, Totzke J, Hughes P, Fox DA, Haystead TAJ. Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice. Arthritis Res Ther. 2019 Dec 17;21(1):292. doi: 10.1186/s13075-019-2073-x. PMID: 31847895; PMCID: PMC6918687. 17: Nagler A, Vredevoogd DW, Alon M, Cheng PF, Trabish S, Kalaora S, Arafeh R, Goldin V, Levesque MP, Peeper DS, Samuels Y. A genome-wide CRISPR screen identifies FBXO42 involvement in resistance toward MEK inhibition in NRAS-mutant melanoma. Pigment Cell Melanoma Res. 2020 Mar;33(2):334-344. doi: 10.1111/pcmr.12825. Epub 2019 Oct 10. PMID: 31549767; PMCID: PMC7383499. 18: Raphemot R, Eubanks AL, Toro-Moreno M, Geiger RA, Hughes PF, Lu KY, Haystead TAJ, Derbyshire ER. Plasmodium PK9 Inhibitors Promote Growth of Liver-Stage Parasites. Cell Chem Biol. 2019 Mar 21;26(3):411-419.e7. doi: 10.1016/j.chembiol.2018.11.003. Epub 2018 Dec 27. PMID: 30595530; PMCID: PMC6430656. 19: Scarneo SA, Mansourati A, Eibschutz LS, Totzke J, Roques JR, Loiselle D, Carlson D, Hughes P, Haystead TAJ. Genetic and pharmacological validation of TAK1 inhibition in macrophages as a therapeutic strategy to effectively inhibit TNF secretion. Sci Rep. 2018 Nov 19;8(1):17058. doi: 10.1038/s41598-018-35189-7. PMID: 30451876; PMCID: PMC6242965. 20: Totzke J, Gurbani D, Raphemot R, Hughes PF, Bodoor K, Carlson DA, Loiselle DR, Bera AK, Eibschutz LS, Perkins MM, Eubanks AL, Campbell PL, Fox DA, Westover KD, Haystead TAJ, Derbyshire ER. Takinib, a Selective TAK1 Inhibitor, Broadens the Therapeutic Efficacy of TNF-α Inhibition for Cancer and Autoimmune Disease. Cell Chem Biol. 2017 Aug 17;24(8):1029-1039.e7. doi: 10.1016/j.chembiol.2017.07.011. PMID: 28820959; PMCID: PMC5576570.