PK68 | CAS#2173556-69-7 | RIPK1 inhibitor

MedKoo Cat#: 462452 | Name: PK68

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Description:

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

PK68 is a potent and selective type II inhibitor of receptor-interacting kinase 1 (RIPK1). It powerfully ameliorates TNF-induced systemic inflammatory response syndrome, and with great potential for use in the treatment of inflammatory disorders and cancer metastasis.

Chemical Structure

PK68

CAS#2173556-69-7

Theoretical Analysis

MedKoo Cat#: 462452

Name: PK68

CAS#: 2173556-69-7

Chemical Formula: C22H24N4O3S

Exact Mass: 424.1569

Molecular Weight: 424.52

Elemental Analysis: C, 62.25; H, 5.70; N, 13.20; O, 11.31; S, 7.55

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Synonym

PK68; PK-68; PK 68

IUPAC/Chemical Name

cyclohexyl (5-(2-acetamidobenzo[d]thiazol-6-yl)-2-methylpyridin-3-yl)carbamate

InChi Key

DRCNWQYEKZTTEW-UHFFFAOYSA-N

InChi Code

InChI=1S/C22H24N4O3S/c1-13-19(26-22(28)29-17-6-4-3-5-7-17)10-16(12-23-13)15-8-9-18-20(11-15)30-21(25-18)24-14(2)27/h8-12,17H,3-7H2,1-2H3,(H,26,28)(H,24,25,27)

SMILES Code

O=C(OC1CCCCC1)NC2=CC(C3=CC=C4N=C(NC(C)=O)SC4=C3)=CN=C2C

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

>3 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

Instruction

View handling instruction

Biological target:

PK68 is a potent orally active and specifical type II inhibitor of receptor-interacting kinase 1 (RIPK1) with an IC50 of ~90 nM.

In vitro activity:

Optimization of PK6 led to PK68, which has improved efficacy for the inhibition of RIPK1-dependent necroptosis, with an EC50 of around 14-22 nM in human and mouse cells. PK68 efficiently blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptosis stimuli. PK68 displays reasonable selectivity for inhibition of RIPK1 kinase activity and favorable pharmacokinetic properties. Reference: Cell Death Dis. 2019 Jun 24;10(7):493. https://pubmed.ncbi.nlm.nih.gov/31235688/

In vivo activity:

This study evaluated the therapeutic effect of PK68 on lung metastasis of mouse melanoma B16-F10 cells in vivo. Notably, pre-treatment of PK68 significantly reduced the number of pulmonary metastasis nodules, suggesting an inhibitory effect of PK68 on metastasis of B16-F10 cells to the lungs in mice (Fig. 8a, b). Consistently, PK68-pre-treated mice showed markedly decreased lung metastasis of RFP-labeled Lewis lung carcinoma LL/2 (RFP-LL/2) cells compared to vehicle-treated mice (Fig. 8c, d). These findings demonstrate that inhibition of RIPK1 by PK68 results in attenuated tumor cell transmigration across the endothelial barrier and preventive suppression of tumor metastasis. Reference: Cell Death Dis. 2019 Jun 24;10(7):493. https://pubmed.ncbi.nlm.nih.gov/31235688/

	Solvent	mg/mL	mM
Solubility
	DMSO	57.5	135.45
	Ethanol	3.0	7.07

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 424.52 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:

Hou J, Ju J, Zhang Z, Zhao C, Li Z, Zheng J, Sheng T, Zhang H, Hu L, Yu X, Zhang W, Li Y, Wu M, Ma H, Zhang X, He S. Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis. Cell Death Dis. 2019 Jun 24;10(7):493. doi: 10.1038/s41419-019-1735-6. PMID: 31235688; PMCID: PMC6591251.

In vitro protocol:

In vivo protocol:

1: Hou J, Ju J, Zhang Z, et al. Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis. Cell Death Dis. 2019;10(7):493. Published 2019 Jun 24. doi:10.1038/s41419-019-1735-6