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MedKoo Cat#: 526661 | Name: MMV390048
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Description:

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

MMV390048, also known as MMV-048, is a novel antimalarial compound belonging to the aminopyridine class. MMV390048 competitively inhibited the binding of only a single protein, P. falciparum PI4 kinase, to the beads. In combination with a partner drug, MMV390048 has the potential to become a new child-friendly treatment for uncomplicated malaria that could be given as one single dose, completing the treatment in just one day instead of the current three days.

Chemical Structure

MMV390048
CAS#1314883-11-8

Theoretical Analysis

MedKoo Cat#: 526661

Name: MMV390048

CAS#: 1314883-11-8

Chemical Formula: C18H14F3N3O2S

Exact Mass: 393.0759

Molecular Weight: 393.38

Elemental Analysis: C, 54.96; H, 3.59; F, 14.49; N, 10.68; O, 8.13; S, 8.15

Price and Availability

Size Price Availability Quantity
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,350.00 Ready to ship
500mg USD 2,950.00 Ready to ship
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Related CAS #
No Data
Synonym
MMV390048; MMV-390048; MMV 390048; MMV-048; MMV 048; MMV048.
IUPAC/Chemical Name
5-(4-(methylsulfonyl)phenyl)-6'-(trifluoromethyl)-[3,3'-bipyridin]-2-amine
InChi Key
RTJQABCNNLMCJF-UHFFFAOYSA-N
InChi Code
InChI=1S/C18H14F3N3O2S/c1-27(25,26)14-5-2-11(3-6-14)13-8-15(17(22)24-10-13)12-4-7-16(23-9-12)18(19,20)21/h2-10H,1H3,(H2,22,24)
SMILES Code
NC1=NC=C(C2=CC=C(S(C)(=O)=O)C=C2)C=C1C3=CN=C(C(F)(F)F)C=C3
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, not in water
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
Biological target:
MMV390048 is a representative of a new chemical class of Plasmodium PI4K inhibitors (Kdapp=0.3 µM) that binds to the ATP binding site of Plasmodium PI4K
In vitro activity:
The in vitro activity of MMV390048 against intraerythrocytic life cycle stages of P. falciparum (NF54 drug-sensitive strain) showed a steep inhibition curve with 50 and 90% inhibitory concentration (IC50 and IC90, respectively) values of 28 and 40 nM, respectively (fig. S1). Against a panel of multidrug-resistant clinical isolates of P. falciparum, the ratio of the maximum/minimum IC50 values for MMV390048 was 1.5-fold, suggesting that MMV390048 has a low risk for cross-resistance (table S1) (10). The prophylactic activity of MMV390048 against the liver stages of Plasmodium that precede symptomatic blood-stage infection was determined in vitro using Plasmodium cynomolgi, a simian parasite species closely related to P. vivax. In a cell-based assay, MMV390048, administered to a primary rhesus hepatocyte cell culture 2 hours after inoculum (allowing sporozoites to invade the hepatocytes), showed potent inhibition of liver-stage development of both schizonts and hypnozoites (fig. S7). The IC50 values were 64 nM for schizonts and 61 nM for hypnozoites (fig. S7). The ability of MMV390048 to block all life cycle stages of the malaria parasite suggests that this compound should be further developed and may contribute to malaria control and eradication as part of a single-dose combination treatment. Reference: Sci Transl Med. 2017 Apr 26; 9(387): eaad9735. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731459/
In vivo activity:
The prophylactic effect of MMV390048 was also evaluated in vivo in P. cynomolgi–infected macaques (Macaca mulatta). Two cohorts of malaria-naïve monkeys were used during this experiment. In cohort 1, MMV390048 (20 mg/kg) was administered orally to three study animals on day 1 before sporozoite inoculation; in cohort 2, two control monkeys were administered orally with the same volume of vehicle. Detectable parasite infection occurred on day 8 after inoculation in the two control monkeys (Fig. 3A). In contrast to the control group, animals from cohort 1 did not present any parasitemia when observed for up to 100 days after inoculation, revealing prophylactic efficacy and full protection by MMV390048 (Fig. 3A, monkeys 3, 4, and 5). To test the host-to-vector-to-host transmission-blocking efficacy of MMV390048 in vivo, a model comprising mouse-to-mosquito-to-mouse transmission of P. berghei infection was used. Within the course of this study, MMV390048 (administered orally at 2 mg/kg) inhibited parasite transmission to the mosquito vector, with a 69.3 and a 30.3% reduction in oocyst intensity (mean number of parasites per midgut) and prevalence (% infected mosquitoes), respectively, observed over two replicate experiments (Table 1 and Fig. 2G). This resulted in a 37.2 and 46.5% reduction in sporozoite intensity and prevalence (Table 1). By fitting data from the mouse-to-mouse assay to a chain binomial model, the effect size of the intervention was estimated, assessing the ability of MMV390048 to reduce the basic reproductive number R0 (assuming 100% coverage). An effect size of 28.5% was estimated [95% confidence interval (CI), 22.8 to 33.7%], suggesting that MMV390048 is capable of acting as a transmission-blocking agent in lower transmission settings. Reference: Sci Transl Med. 2017 Apr 26; 9(387): eaad9735. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731459/
Solvent mg/mL mM comments
Solubility
Soluble in DMSO 0.0 0.00
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 393.38 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.

Recalculate based on batch purity %
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. Paquet T, Le Manach C, Cabrera DG, Younis Y, Henrich PP, Abraham TS, Lee MCS, Basak R, Ghidelli-Disse S, LafuenteMonasterio MJ, Bantscheff M, Ruecker A, Blagborough AM, Zakutansky SE, Zeeman AM, White KL, Shackleford DM, Mannila J, Morizzi J, Scheurer C, Angulo-Barturen I, Martínez MS, Ferrer S, Sanz LM, Gamo FJ, Reader J, Botha M, Dechering KJ, Sauerwein RW, Tungtaeng A, Vanachayangkul P, Lim CS, Burrows J, Witty MJ, Marsh KC, Bodenreider C, Rochford R, Solapure SM, Jiménez-Díaz MB, Wittlin S, Charman SA, Donini C, Campo B, Birkholtz LM, Hanson KK, Drewes G, Kocken CHM, Delves MJ, Leroy D, Fidock DA, Waterson D, Street LJ, Chibale K. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med. 2017 Apr 26;9(387):eaad9735. doi: 10.1126/scitranslmed.aad9735. PMID: 28446690; PMCID: PMC5731459.
In vitro protocol:
1. Paquet T, Le Manach C, Cabrera DG, Younis Y, Henrich PP, Abraham TS, Lee MCS, Basak R, Ghidelli-Disse S, LafuenteMonasterio MJ, Bantscheff M, Ruecker A, Blagborough AM, Zakutansky SE, Zeeman AM, White KL, Shackleford DM, Mannila J, Morizzi J, Scheurer C, Angulo-Barturen I, Martínez MS, Ferrer S, Sanz LM, Gamo FJ, Reader J, Botha M, Dechering KJ, Sauerwein RW, Tungtaeng A, Vanachayangkul P, Lim CS, Burrows J, Witty MJ, Marsh KC, Bodenreider C, Rochford R, Solapure SM, Jiménez-Díaz MB, Wittlin S, Charman SA, Donini C, Campo B, Birkholtz LM, Hanson KK, Drewes G, Kocken CHM, Delves MJ, Leroy D, Fidock DA, Waterson D, Street LJ, Chibale K. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med. 2017 Apr 26;9(387):eaad9735. doi: 10.1126/scitranslmed.aad9735. PMID: 28446690; PMCID: PMC5731459.
In vivo protocol:
1. Paquet T, Le Manach C, Cabrera DG, Younis Y, Henrich PP, Abraham TS, Lee MCS, Basak R, Ghidelli-Disse S, LafuenteMonasterio MJ, Bantscheff M, Ruecker A, Blagborough AM, Zakutansky SE, Zeeman AM, White KL, Shackleford DM, Mannila J, Morizzi J, Scheurer C, Angulo-Barturen I, Martínez MS, Ferrer S, Sanz LM, Gamo FJ, Reader J, Botha M, Dechering KJ, Sauerwein RW, Tungtaeng A, Vanachayangkul P, Lim CS, Burrows J, Witty MJ, Marsh KC, Bodenreider C, Rochford R, Solapure SM, Jiménez-Díaz MB, Wittlin S, Charman SA, Donini C, Campo B, Birkholtz LM, Hanson KK, Drewes G, Kocken CHM, Delves MJ, Leroy D, Fidock DA, Waterson D, Street LJ, Chibale K. Antimalarial efficacy of MMV390048, an inhibitor of Plasmodium phosphatidylinositol 4-kinase. Sci Transl Med. 2017 Apr 26;9(387):eaad9735. doi: 10.1126/scitranslmed.aad9735. PMID: 28446690; PMCID: PMC5731459.
Identification of Plasmodium PI4 kinase as target of MMV390048 by chemoproteomics Sonja Ghidelli-Disse, Maria Jose Lafuente-Monasterio, David Waterson, Michael Witty, Yassir Younis, Tanya Paquet, Leslie J Street, Kelly Chibale, Francisco Javier Gamo-Benito, Marcus Bantscheff and Gerard Drewes Malaria Journal201413(Suppl 1):P38 DOI: 10.1186/1475-2875-13-S1-P38