PF-06260933| CAS#1811510-56-1 | MAP4K4 inhibitor

MedKoo Cat#: 527680 | Name: PF-06260933

Description:

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

PF-06260933 is a potent and highly selective inhibitor of MAP4K4.

Chemical Structure

PF-06260933

CAS#1811510-56-1 (free base)

Theoretical Analysis

MedKoo Cat#: 527680

Name: PF-06260933

CAS#: 1811510-56-1 (free base)

Chemical Formula: C16H13ClN4

Exact Mass: 296.0829

Molecular Weight: 296.76

Elemental Analysis: C, 64.76; H, 4.42; Cl, 11.95; N, 18.88

Price and Availability

Size	Price	Availability
100mg	USD 550.00	2 Weeks
200mg	USD 950.00	2 Weeks
500mg	USD 1,950.00	2 Weeks
1g	USD 2,950.00	2 Weeks
2g	USD 5,250.00	2 Weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

1883548-86-4 (2HCl) 1811510-56-1 (free base) 2118243-34-6 (HCl)

Synonym

PF06260933; PF 06260933; PF-06260933; PF6260933; PF 6260933; PF-6260933;

IUPAC/Chemical Name

5-(4-Chlorophenyl)-[3,3']bipyridinyl-6,6'-diamine

InChi Key

KHPCIHZXOGHCLY-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H13ClN4/c17-13-4-1-10(2-5-13)14-7-12(9-21-16(14)19)11-3-6-15(18)20-8-11/h1-9H,(H2,18,20)(H2,19,21)

SMILES Code

NC1=C(C2=CC=C(Cl)C=C2)C=C(C3=CC=C(N)N=C3)C=N1

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

Instruction

View handling instruction

Biological target:

PF-06260933 is an orally active and highly selective inhibitor of MAP4K4 with IC50s of 3.7 and 160 nM for kinase and cell.

In vitro activity:

To optimize the hydrogen bond with Asp115, compound 16 (PF-06260933) was prepared, as modeling indicated that the NH2 group of the newly introduced aminopyridine group interacts with Asp115 in a similar fashion as the phenol OH in 13. Compound 16 (PF-6260933) was very potent against the enzyme with a very good ligand efficiency (LE = 0.57) and was the most potent analogue in the cell assay. Indeed, compound 16 showed a kinase activity IC50 (tested at Km) of 15 and 8 nM for TNIK and MINK, respectively. Reference: ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. https://pubmed.ncbi.nlm.nih.gov/26617966/

In vivo activity:

The model mice were assigned to four groups: MAP4K4 recombinant protein, scramble small interfering RNA, and MAP4K4 small interfering RNA were delivered by intracerebroventricular injection, while PF-06260933, a small-molecule inhibitor of MAP4K4, was administrated orally. Furthermore, administration of the MAP4K4 inhibitor PF-06260933 reduced blood-brain barrier damage in mice, promoted the recovery of neurological function, and reduced p-p65 and MMP9 protein expression. Reference: Neural Regen Res. 2021 Feb;16(2):325-332. https://pubmed.ncbi.nlm.nih.gov/32859792/

	Solvent	mg/mL	mM
Solubility
	DMF	1.0	3.37
	DMSO	30.0	101.09
	Ethanol	2.0	6.74

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 296.76 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. Zou Z, Dong YS, Liu DD, Li G, Hao GZ, Gao X, Pan PY, Liang GB. MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model. Neural Regen Res. 2021 Feb;16(2):325-332. doi: 10.4103/1673-5374.290904. PMID: 32859792; PMCID: PMC7896238. 2. Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A, Ford K, Guimarães CR, Hepworth D, Jiao W, LaPerle J, Liu S, Londregan A, Loria PM, Mathiowetz AM, Munchhof M, Orr ST, Petersen DN, Price DA, Skoura A, Smith AC, Wang J. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. doi: 10.1021/acsmedchemlett.5b00215. PMID: 26617966; PMCID: PMC4645242.

In vitro protocol:

1. Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A, Ford K, Guimarães CR, Hepworth D, Jiao W, LaPerle J, Liu S, Londregan A, Loria PM, Mathiowetz AM, Munchhof M, Orr ST, Petersen DN, Price DA, Skoura A, Smith AC, Wang J. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. doi: 10.1021/acsmedchemlett.5b00215. PMID: 26617966; PMCID: PMC4645242.

In vivo protocol:

1: Yang J, Zheng XG, Wu YL, Wang AP, Wang CH, Chen WX, Zhong S, Yang H. Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4. Biomed Pharmacother. 2022 May;149:112810. doi: 10.1016/j.biopha.2022.112810. Epub 2022 Mar 15. PMID: 35303564. 2: Nam GS, Kim S, Kwon YS, Kim MK, Nam KS. A new function for MAP4K4 inhibitors during platelet aggregation and platelet-mediated clot retraction. Biochem Pharmacol. 2021 Jun;188:114519. doi: 10.1016/j.bcp.2021.114519. Epub 2021 Mar 15. PMID: 33737052. 3: Zou Z, Dong YS, Liu DD, Li G, Hao GZ, Gao X, Pan PY, Liang GB. MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model. Neural Regen Res. 2021 Feb;16(2):325-332. doi: 10.4103/1673-5374.290904. PMID: 32859792; PMCID: PMC7896238. 4: Roth Flach RJ, Skoura A, Matevossian A, Danai LV, Zheng W, Cortes C, Bhattacharya SK, Aouadi M, Hagan N, Yawe JC, Vangala P, Menendez LG, Cooper MP, Fitzgibbons TP, Buckbinder L, Czech MP. Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nat Commun. 2015 Dec 21;6:8995. doi: 10.1038/ncomms9995. PMID: 26688060; PMCID: PMC4703891. 5: Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A, Ford K, Guimarães CR, Hepworth D, Jiao W, LaPerle J, Liu S, Londregan A, Loria PM, Mathiowetz AM, Munchhof M, Orr ST, Petersen DN, Price DA, Skoura A, Smith AC, Wang J. Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett. 2015 Oct 6;6(11):1128-33. doi: 10.1021/acsmedchemlett.5b00215. PMID: 26617966; PMCID: PMC4645242.