Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C47H54N6O3 |
Molecular Weight | 750.9701 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CC(=O)N1CCN(CC1)C2=CC=C(CN([C@@H](CC3=CC=CC=C3)C(=O)N4CCN(CC5=CC=C(C=C5)C#N)CC4)C(=O)\C=C\C6=CC=C(C=C6)C(C)(C)C)C=C2
InChI
InChIKey=BQZUYCCCNXOADJ-TVNMEPFQSA-N
InChI=1S/C47H54N6O3/c1-36(54)50-28-30-51(31-29-50)43-21-16-41(17-22-43)35-53(45(55)23-18-37-14-19-42(20-15-37)47(2,3)4)44(32-38-8-6-5-7-9-38)46(56)52-26-24-49(25-27-52)34-40-12-10-39(33-48)11-13-40/h5-23,44H,24-32,34-35H2,1-4H3/b23-18+/t44-/m0/s1
Molecular Formula | C47H54N6O3 |
Molecular Weight | 750.9701 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 1 |
Optical Activity | UNSPECIFIED |
ACT-451840 is a new compound with potent activity against sensitive and resistant Plasmodium falciparum strains. ACT-451840 has been used in trials studying malaria. ACT-451840 appears to have a distinct mode of action that sets it apart from current antimalarial drugs, including artemisinins. It has a rapid onset of action as well as activity on all blood-borne (erythrocytic) stages, which is retained against multiple resistant parasites, including artemisinin-resistant strains. Unlike the majority of antimalarial agents, ACT-451840 has the potential to block disease transmission due to its activity on gametocytes. he antimalarial activity of ACT-451840 was studied in an experimental induced blood stage malaria clinical trial performed in collaboration with MMV Medicines for Malaria Ventures at the laboratories of Professor James McCarthy, MBBS, MD of the Royal Brisbane and Women's Hospital in Herston, Australia. In the trial, ACT-451840 was safe and well tolerated and showed clinical efficacy against the early stages of P. falciparum infections. The PK/PD model developed from this proof-of-concept study with eight healthy subjects enabled prediction of therapeutic effects, with cure rates following 1 week of therapy (single daily doses) predicted to be equivalent to artesunate monotherapy.
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25421475
This was a first-in-humans single-ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of ACT-451840 across doses of 10, 50, 200, and 500 mg in healthy male subjects. In the 200- and 500-mg dose groups, the effect of food was investigated, and antimalarial activity was assessed using an ex vivo bioassay with P. falciparum.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27701420
In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39).
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:04:45 GMT 2023
by
admin
on
Sat Dec 16 11:04:45 GMT 2023
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Record UNII |
FO890BDO84
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Record Status |
Validated (UNII)
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Record Version |
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1314143-88-8
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FO890BDO84
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53303762
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300000041384
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DB13054
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