[CAS NO. 1832576-04-1] MLT-943
PRODUCTS SPECIFICATIONS [1832576-04-1]
DESCRIPTION [1832576-04-1]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 414.77 |
| Molecular Formula | C16H14ClF3N6O2 |
| SMILES | CO[C@H](C1=C(NC(NC2=CC=NC(C(F)(F)F)=C2)=O)C=NC3=CC(Cl)=NN13)C |
Summary
MLT-943 is a potent, selective and orally active MALT1 protease inhibitor. MLT-943 inhibits stimulated-IL-2 secretion in PBMC or in whole blood with a similar IC 50 across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood). MLT-943 has anti-inflammatory activities and can be used for FcgR-mediated inflammation research [1] .
In Vitro
MLT-943 shows a high potency and selectivity
in vitro
. MLT-943 inhibits stimulated IL-2 secretion in PBMC or in whole blood with a similar IC
50
across species (0.07-0.09 μM in PBMC, 0.6-0.8 μM in whole blood)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
MLT-943 (oral gavage; 10 mg/kg; QD) prophylactic treatment in the rat collagen-induced arthritis model suppresses anti-collagen antibody production, fully prevents paw swelling, and normalizes joint histology scores in rat model
[1]
.
MLT-943 (oral gavage; 5 mg/kg; QD; 10 consecutive days) effectively inhibits MALT1 protease activity and results in a progressive reduction in the frequency of Foxp
3+
CD25
+
Treg cells in circulating CD4
+
T cells, which was maximal after 7 days of treatment. And Discontinuation of MLT-943 treatment after day 10 leads to Treg frequency progressively returning to their original values within 4 days. Suboptimal doses of MLT-943 (0.1 and 0.5 mg/kg QD; p.o.) does not impact the Treg frequency
[1]
.
MLT-943 (oral gavage; 0, 5, 20 or 80 mg/kg/day; 4-13 weeks) causes a reduction in Treg and an increase in total T cell counts, in both 4- and 13-week rat toxicity studies at all dose levels. While a 4-Longer treatment induces severe immune-mediated pathology in multiple organs, with clinical onset starting around week 9 in rat
[1]
.
MLT-943 (p.o. admistration; 3 mg/kg; single dose) exhibits a good PK parameters
in vivo
. The C
max
values are 0.7 nM and 0.5 nM, respectively in rat and mice, respectively. And the F% are 86% and 50% in rat and mice, respective
[1]
.
For i.v. admistration the compound is formed in NMP:PEG200 (30/70); For p.o. admistration solution is formed in MC:Tween 80:Water (0.5:0.5:99) solution (Sourced from literature, for reference only)
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Naïve rats [1] |
| Dosage: | 5 mg/kg |
| Administration: | Oral gavage; 5 mg/kg, 10 consecutive days or 0.1 mg/kg MLT-943 |
| Result: | Induced a severe immune-mediated pathology after a prolonged treatment |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 250 mg/mL ( 602.74 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.4110 mL | 12.0549 mL | 24.1097 mL |
| 5 mM | 0.4822 mL | 2.4110 mL | 4.8219 mL |
| 10 mM | 0.2411 mL | 1.2055 mL | 2.4110 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.08 mg/mL (5.01 mM); Clear solution
References
- [1] Kea Martin, et al. Pharmacological Inhibition of MALT1 Protease Leads to a Progressive IPEX-Like Pathology. Front Immunol
- [2] Jean Quancard, et al. Optimization of the In Vivo Potency of Pyrazolopyrimidine MALT1 Protease Inhibitors by Reducing Metabolism and Increasing Potency in Whole Blood. J Med Chem. 2020 Dec 10;63(23):14594-14608.