MW-150 | CAS#1628502-91-9 | p38α MAPK inhibitor

MW-150
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 534847

CAS#: 1628502-91-9

Description: MW-150 is an inhibitor of p38α MAPK (Ki = 101 nM). It is 6-, 10-, and 14-fold selective for p38α MAPK over the serine/threonine protein kinase NLK, p38β MAPK, and p38δ MAPK, respectively, and is also selective over the enzymatically normal mutant p38α MAPKT106M. It inhibits p38α MAPK phosphorylation of the endogenous substrate MAPK-activated protein kinase 2 (MK2) in LPS-activated glia in a concentration-dependent manner and decreases the levels of IL-1β in the same cells. MW-150 (2.5 mg/kg per day, i.p.) reduces the number of errors made in the spatial reference memory version of the radial arm water maze in aged amyloid precursor protein/presenilin 1 (APP/PS1) knock-in mice as a model of Alzheimer’s disease.

Chemical Structure

MW-150

CAS# 1628502-91-9

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 534847
Name: MW-150
CAS#: 1628502-91-9
Chemical Formula: C24H25N5
Exact Mass: 383.21
Molecular Weight: 383.499
Elemental Analysis: C, 75.17; H, 6.57; N, 18.26

Price and Availability

Size	Price	Availability
1mg	USD 265	2 Weeks
5mg	USD 700	2 Weeks
10mg	USD 1150	2 Weeks
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: MW-150; MW 150; MW150; MW01-18-150SRM;

IUPAC/Chemical Name: 6-(4-Methyl-piperazin-1-yl)-(2-naphthalen-2-yl)-4-pyridin-4-ylpyridazine

InChi Key: GCXKBBPMNOZOJS-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H25N5/c1-27-12-14-28(15-13-27)24-17-22(20-8-10-25-11-9-20)18-29(26-24)23-7-6-19-4-2-3-5-21(19)16-23/h2-11,16-18,26H,12-15H2,1H3

SMILES Code: CN1CCN(C2=CC(C3=CC=NC=C3)=CN(C4=CC=C5C=CC=CC5=C4)N2)CC1

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:

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Biological target:	MW150 (MW01-18-150SRM) is a selective, CNS penetrant, and orally active inhibitor of p38α MAPK with a Ki of 101 nM.
In vitro activity:	As summarized herein, a final optimization by synthesis and screening yielded MW150 that has improved HLM stability (T1/2 > 60 min) and oral bioavailability (>50%) as well as an incrementally improved p38αMAPK inhibition activity with retention of target selectivity, safety, and brain penetrance. MW150, containing a R3 piperazine substituent and R6 2-naphthyl substituent, represents the best in class for metabolic and bioavailability potential with retention of isoform selective p38αMAPK IC50 activity. Reference: ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. https://pubmed.ncbi.nlm.nih.gov/25676389/
In vivo activity:	Strikingly, 1-week treatment of adult SERT Ala56 mice with MW150, a selective p38α MAPK inhibitor, normalized hippocampal 5-HT clearance, CNS 5-HT1A and 5-HT2A/2C receptor sensitivities, social interactions, and colonic motility. Conditional elimination of p38α MAPK in 5-HT neurons of SERT Ala56 mice restored 5-HT1A and 5-HT2A/2C receptor sensitivities as well as social interactions, mirroring effects of MW150. Reference: Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10245-E10254. https://pubmed.ncbi.nlm.nih.gov/30297392/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	15.0	39.10
	DMF:PBS (pH 7.2) (1:3)	0.3	0.65
	DMSO	1.0	2.60
	Ethanol	1.0	2.60

Preparing Stock Solutions

The following data is based on the product molecular weight 383.50 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. Roy SM, Grum-Tokars VL, Schavocky JP, Saeed F, Staniszewski A, Teich AF, Arancio O, Bachstetter AD, Webster SJ, Van Eldik LJ, Minasov G, Anderson WF, Pelletier JC, Watterson DM. Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. doi: 10.1021/acschemneuro.5b00002. Epub 2015 Feb 23. PMID: 25676389; PMCID: PMC4404319. 2. Robson MJ, Quinlan MA, Margolis KG, Gajewski-Kurdziel PA, Veenstra-VanderWeele J, Gershon MD, Watterson DM, Blakely RD. p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10245-E10254. doi: 10.1073/pnas.1809137115. Epub 2018 Oct 8. PMID: 30297392; PMCID: PMC6205438. 3. Rutigliano G, Stazi M, Arancio O, Watterson DM, Origlia N. An isoform-selective p38α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease. Neurobiol Aging. 2018 Oct;70:86-91. doi: 10.1016/j.neurobiolaging.2018.06.006. Epub 2018 Jun 12. PMID: 30007168; PMCID: PMC6119125.
In vitro protocol:	1. Roy SM, Grum-Tokars VL, Schavocky JP, Saeed F, Staniszewski A, Teich AF, Arancio O, Bachstetter AD, Webster SJ, Van Eldik LJ, Minasov G, Anderson WF, Pelletier JC, Watterson DM. Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. doi: 10.1021/acschemneuro.5b00002. Epub 2015 Feb 23. PMID: 25676389; PMCID: PMC4404319.
In vivo protocol:	1. Robson MJ, Quinlan MA, Margolis KG, Gajewski-Kurdziel PA, Veenstra-VanderWeele J, Gershon MD, Watterson DM, Blakely RD. p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10245-E10254. doi: 10.1073/pnas.1809137115. Epub 2018 Oct 8. PMID: 30297392; PMCID: PMC6205438. 2. Rutigliano G, Stazi M, Arancio O, Watterson DM, Origlia N. An isoform-selective p38α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease. Neurobiol Aging. 2018 Oct;70:86-91. doi: 10.1016/j.neurobiolaging.2018.06.006. Epub 2018 Jun 12. PMID: 30007168; PMCID: PMC6119125.

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1: Roy SM, Minasov G, Arancio O, Chico LW, Van Eldik LJ, Anderson WF, Pelletier JC, Watterson DM. A Selective and Brain Penetrant p38αMAPK Inhibitor Candidate for Neurologic and Neuropsychiatric Disorders That Attenuates Neuroinflammation and Cognitive Dysfunction. J Med Chem. 2019 Jun 13;62(11):5298-5311. doi: 10.1021/acs.jmedchem.9b00058. Epub 2019 Apr 23. Erratum in: J Med Chem. 2020 Aug 13;63(15):8649. PMID: 30978288; PMCID: PMC6580366.

2: Robson MJ, Quinlan MA, Margolis KG, Gajewski-Kurdziel PA, Veenstra- VanderWeele J, Gershon MD, Watterson DM, Blakely RD. p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10245-E10254. doi: 10.1073/pnas.1809137115. Epub 2018 Oct 8. PMID: 30297392; PMCID: PMC6205438.

3: Rutigliano G, Stazi M, Arancio O, Watterson DM, Origlia N. An isoform- selective p38α mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer's disease. Neurobiol Aging. 2018 Oct;70:86-91. doi: 10.1016/j.neurobiolaging.2018.06.006. Epub 2018 Jun 12. PMID: 30007168; PMCID: PMC6119125.

4: Zhou Z, Bachstetter AD, Späni CB, Roy SM, Watterson DM, Van Eldik LJ. Retention of normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes. J Neuroinflammation. 2017 Apr 5;14(1):75. doi: 10.1186/s12974-017-0845-2. PMID: 28381303; PMCID: PMC5382362.

5: Roy SM, Grum-Tokars VL, Schavocky JP, Saeed F, Staniszewski A, Teich AF, Arancio O, Bachstetter AD, Webster SJ, Van Eldik LJ, Minasov G, Anderson WF, Pelletier JC, Watterson DM. Targeting human central nervous system protein kinases: An isoform selective p38αMAPK inhibitor that attenuates disease progression in Alzheimer's disease mouse models. ACS Chem Neurosci. 2015 Apr 15;6(4):666-80. doi: 10.1021/acschemneuro.5b00002. Epub 2015 Feb 23. PMID: 25676389; PMCID: PMC4404319.

6: Deloye F, Doussau F, Poulain B. Mécanismes d'action des neurotoxines botuliques et de la neurotoxine tétanique [Action mechanisms of botulinum neurotoxins and tetanus neurotoxins]. C R Seances Soc Biol Fil. 1997;191(3):433-50. French. PMID: 9295967.

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MW-150 featured