Name: Neflamapimod (VX-745)
Brand: Selleck Chemicals
SKU: S1458
Availability: InStock
Rating: 5 (13 reviews)

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Quality Control

Batch: Purity: 99.98%

99.98

Related Targets	ERK Raf JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other p38 MAPK Inhibitors	SB202190 SB203580 (Adezmapimod) PH-797804 Doramapimod (BIRB 796) Ralimetinib (LY2228820) dimesylate VX-702 Losmapimod SB239063 BMS-582949 Skepinone-L

Solubility

In vitro
Batch:

DMSO : 15 mg/mL (34.38 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	30%PEG400 1 0.5%Tween80 2 5%propylene glycol Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	30.000mg/ml (68.77mM)	Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

+

%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	436.26	Formula	C₁₉H₉Cl₂F₂N₃OS	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	209410-46-8	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	C1=CC(=C(C(=C1)Cl)C2=C3C=CC(=NN3C=NC2=O)SC4=C(C=C(C=C4)F)F)Cl

Mechanism of Action

Features	A potent and selective inhibitor to p38α and p38β MAPK.
Targets/IC₅₀/Ki	p38α 10 nM p38β 220 nM
In vitro	Neflamapimod (VX-745) selectively inhibits p38α and p38β MAPK with IC50 of 10 nM and 220 nM, respectively, but not p38γ MAPK and a large panel of other kinases, with IC50 larger than 20 µM. In a human peripheral blood mononuclear cell (PBMC) assay, it provides IC50 of 56 and 52 nM for IL-1β and TNFα, respectively. This compound blocks IL-6 and IL-8 production induced by IL-1 and TNFα, and COX-2 synthesis mediated by LPS and IL-1β. At concentrations of 60 nM-20 µM, it inhibits IL-6 and VEGF secretion in bone marrow stromal cells (BMSCs), without affecting their viability. It also inhibits TNF-α-induced IL-6 secretion in BMSCs. Furthermore, it inhibits both multiple myeloma (MM) cell proliferation and IL-6 secretion in BMSCs triggered by adherence of MM cells to BMSCs, suggesting that VX-745 can inhibit paracrine multiple myeloma (MM) cell growth in the BM milieu and overcome cell adhesion-related drug resistance.
Kinase Assay	Spectrophotometric coupled-enzyme assay
Kinase Assay	Neflamapimod (VX-745) 的 IC50 值通过分光光度法偶联酶测定获得，用于抑制 p38α 和 p38β 同源蛋白。将固定浓度的酶（15 nM p38α 或 p38β）与该化合物在 DMSO 中于 30 °C 孵育 10 分钟，缓冲液为 0.1 M HEPES（pH 7.5），含 10% 甘油、10 mM MgCl₂、2.5 mM 磷酸烯醇丙酮酸、200 µM NADH、150 µg/mL 丙酮酸激酶、50 µg/mL 乳酸脱氢酶和 200 µM EGF 受体肽（KRELVEPLTPSGEAPNQALLR）。反应分别通过加入 100 µM（p38α 测定）和 70 µM（p38β 测定）的 ATP 启动。通过监测 340 nm 处吸光度的降低来跟踪反应速率，IC50 值根据速率数据随该抑制剂浓度的函数关系评估得出。
In vivo	Neflamapimod (VX-745) is effective against adjuvant-induced arthritis (AA) in the rat with ED50 of 5 mg/kg. Histological scores for this compound in AA rats are 93% inhibition of bone resorption and 56% inhibition of inflammation. In the classical cartilage-induced arthritis model, it exhibits a dose-responsive decrease in severity score. In a type II collagen-induced arthritis (CIA) mice model, VX-745 (2.5, 5, and 10 mg/kg) has 27%, 31%, and 44% improvement in the inflammatory scores, respectively, when compared to vehicle-treated mice. In addition, histological scores show a 32-39% protection of bone and cartilage erosion by it.
References	[1] # [2] https://pubmed.ncbi.nlm.nih.gov/11892915/ [3] # [4] https://pubmed.ncbi.nlm.nih.gov/12393542/ [5] http://pubs.acs.org/doi/abs/10.1021/ml2001455

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02423200	Completed	Alzheimer''s Disease	EIP Pharma Inc	April 2015	Phase 2

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Neflamapimod (VX-745) p38 MAPK inhibitor

Chemical Structure

Molecular Weight: 436.26