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
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
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/
|
Solvent |
mg/mL |
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 |
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
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.
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.
