ACT-451840 | CAS#1984890-99-4 | Antimalarial drug

MedKoo Cat#: 571533 | Name: ACT-451840

Description:

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

ACT-451840 is a drug that exhibits antimalarial activity. It has potent activity against sensitive and resistant Plasmodium falciparum strains. Note: Its CAS# was previously listed as 1839508-99-4.

Chemical Structure

ACT-451840

CAS#1984890-99-4 (S-isomer)

Theoretical Analysis

MedKoo Cat#: 571533

Name: ACT-451840

CAS#: 1984890-99-4 (S-isomer)

Chemical Formula: C47H54N6O3

Exact Mass: 750.4257

Molecular Weight: 750.99

Elemental Analysis: C, 75.17; H, 7.25; N, 11.19; O, 6.39

Price and Availability

Size	Price	Availability
1mg	USD 80.00	Ready to ship
5mg	USD 250.00	Ready to ship
10mg	USD 400.00	Ready to ship
25mg	USD 850.00	Ready to ship
50mg	USD 1,350.00	Ready to ship
100mg	USD 2,150.00	Ready to ship

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Related CAS #

1984890-99-4 (S-isomer) 1839508-99-4 (racemic)

Synonym

ACT-451840; ACT451840; ACT 451840

IUPAC/Chemical Name

(2E)-N-[[4-(4-Acetyl-1-piperazinyl)phenyl]methyl]-N-[(1S)-2-[4-[(4-cyanophenyl)methyl]-1-piperazinyl]-2-oxo-1-(phenylmethyl)ethyl]-3-[4-(1,1-dimethylethyl)phenyl]-2-propenamide

InChi Key

BQZUYCCCNXOADJ-TVNMEPFQSA-N

InChi Code

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

SMILES Code

O=C(N(CC1=CC=C(N2CCN(C(C)=O)CC2)C=C1)[C@@H](CC3=CC=CC=C3)C(N4CCN(CC5=CC=C(C#N)C=C5)CC4)=O)/C=C/C6=CC=C(C(C)(C)C)C=C6

Appearance

Solid powder

Purity

>96% (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

>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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T22D01P19

QC Data

View QC data: current batch, Lot#T22D01P19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

ACT-451840 shows a 50 % inhibition concentration of 0.4 nM against the drug-sensitive P. falciparum NF54 strain. The IC50 value of ACT-451840 against the murine malaria parasite P. berghei is 13.5 nM in in vitro ex vivo assays.

In vitro activity:

In summary, ACT-451840 had an IC50 below 10 nM in vitro against a panel of sensitive and resistant strains of P. falciparum and was fully active against recently identified artemisinin-resistant strains. Furthermore, the compound showed ex vivo activity against P. falciparum and P. vivax as well as a single digit mg/kg ED90 in a P. falciparum murine model. In addition, the compound inhibited growth of all asexual blood stages of P. falciparum in vitro, and its in vitro PRR was similar to that of chloroquine. Reference: PLoS Med. 2016 Oct 4;13(10):e1002138. https://pubmed.ncbi.nlm.nih.gov/27701420/

In vivo activity:

	Solvent	mg/mL	mM
Solubility
	DMSO	41.7	55.49

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 750.99 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. Le Bihan A, de Kanter R, Angulo-Barturen I, Binkert C, Boss C, Brun R, Brunner R, Buchmann S, Burrows J, Dechering KJ, Delves M, Ewerling S, Ferrer S, Fischli C, Gamo-Benito FJ, Gnädig NF, Heidmann B, Jiménez-Díaz MB, Leroy D, Martínez MS, Meyer S, Moehrle JJ, Ng CL, Noviyanti R, Ruecker A, Sanz LM, Sauerwein RW, Scheurer C, Schleiferboeck S, Sinden R, Snyder C, Straimer J, Wirjanata G, Marfurt J, Price RN, Weller T, Fischli W, Fidock DA, Clozel M, Wittlin S. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. PLoS Med. 2016 Oct 4;13(10):e1002138. doi: 10.1371/journal.pmed.1002138. PMID: 27701420; PMCID: PMC5049785.

In vitro protocol:

In vivo protocol:

1: Boss C, Wittlin S. Our Exciting Journey to ACT-451840. Chimia (Aarau). 2021 Nov 24;75(11):916-922. doi: 10.2533/chimia.2021.916. PMID: 34798913. 2: Le Bihan A, de Kanter R, Angulo-Barturen I, Binkert C, Boss C, Brun R, Brunner R, Buchmann S, Burrows J, Dechering KJ, Delves M, Ewerling S, Ferrer S, Fischli C, Gamo-Benito FJ, Gnädig NF, Heidmann B, Jiménez-Díaz MB, Leroy D, Martínez MS, Meyer S, Moehrle JJ, Ng CL, Noviyanti R, Ruecker A, Sanz LM, Sauerwein RW, Scheurer C, Schleiferboeck S, Sinden R, Snyder C, Straimer J, Wirjanata G, Marfurt J, Price RN, Weller T, Fischli W, Fidock DA, Clozel M, Wittlin S. Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling. PLoS Med. 2016 Oct 4;13(10):e1002138. doi: 10.1371/journal.pmed.1002138. PMID: 27701420; PMCID: PMC5049785. 3: Boss C, Aissaoui H, Amaral N, Bauer A, Bazire S, Binkert C, Brun R, Bürki C, Ciana CL, Corminboeuf O, Delahaye S, Dollinger C, Fischli C, Fischli W, Flock A, Frantz MC, Girault M, Grisostomi C, Friedli A, Heidmann B, Hinder C, Jacob G, Le Bihan A, Malrieu S, Mamzed S, Merot A, Meyer S, Peixoto S, Petit N, Siegrist R, Trollux J, Weller T, Wittlin S. Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action. ChemMedChem. 2016 Sep 20;11(18):1995-2014. doi: 10.1002/cmdc.201600298. Epub 2016 Jul 29. PMID: 27471138. 4: Bruderer S, Hurst N, de Kanter R, Miraval T, Pfeifer T, Donazzolo Y, Dingemanse J. First-in-humans study of the safety, tolerability, and pharmacokinetics of ACT-451840, a new chemical entity with antimalarial activity. Antimicrob Agents Chemother. 2015 Feb;59(2):935-42. doi: 10.1128/AAC.04125-14. Epub 2014 Nov 24. PMID: 25421475; PMCID: PMC4335896. 5: Ng CL, Siciliano G, Lee MC, de Almeida MJ, Corey VC, Bopp SE, Bertuccini L, Wittlin S, Kasdin RG, Le Bihan A, Clozel M, Winzeler EA, Alano P, Fidock DA. CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs. Mol Microbiol. 2016 Aug;101(3):381-93. doi: 10.1111/mmi.13397. Epub 2016 May 7. PMID: 27073104; PMCID: PMC4958522. 6: Boss C. 20 Years of Medicinal Chemistry - Always Look at the Bright Side (of Life). Chimia (Aarau). 2020 Aug 12;74(7):549-560. doi: 10.2533/chimia.2020.549. PMID: 32778207. 7: Krause A, Dingemanse J, Mathis A, Marquart L, Möhrle JJ, McCarthy JS. Pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of Actelion-451840 in an induced blood stage malaria study in healthy subjects. Br J Clin Pharmacol. 2016 Aug;82(2):412-21. doi: 10.1111/bcp.12962. Epub 2016 May 11. PMID: 27062080; PMCID: PMC4972157. 8: Chughlay MF, Akakpo S, Odedra A, Csermak-Renner K, Djeriou E, Winnips C, Leboulleux D, Gaur AH, Shanks GD, McCarthy J, Chalon S. Liver Enzyme Elevations in Plasmodium falciparum Volunteer Infection Studies: Findings and Recommendations. Am J Trop Med Hyg. 2020 Jul;103(1):378-393. doi: 10.4269/ajtmh.19-0846. Epub 2020 Apr 16. PMID: 32314694; PMCID: PMC7356411.