[CAS NO. 2751586-94-2] Ganaplacide hydrochloride
PRODUCTS SPECIFICATIONS [2751586-94-2]
DESCRIPTION [2751586-94-2]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 447.91 |
| Molecular Formula | C22H24ClF2N5O |
| SMILES | FC(C=C1)=CC=C1C2=C(N3C(C(C)(N(C(CN)=O)CC3)C)=N2)NC4=CC=C(F)C=C4.[H]Cl |
Summary
Ganaplacide (KAF156) hydrochloride is a first-in-class, orally active imidazolopiperazine antimalarial agent. Ganaplacide hydrochloride is active against a broad range of Plasmodium species, including drug-resistant parasites. Ganaplacide hydrochloride is parasiticidal against both asexual and sexual blood stages as well as the liver stages of the parasite [1] [2] .
IC50 & Target
|
Plasmodium |
In Vitro
Ganaplacide (KAF156) hydrochloride shows blood schizonticidal activity with 50% inhibitory concentrations of 6 to 17.4 nM against P. falciparum drug-sensitive and drug-resistant strains [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
KAF156 displays cidal activity against mature
Plasmodium falciparum
gametocytes and thus blocks parasite transmission to
Anopheles
mosquitoes
[1]
.
Ganaplacide (KAF156) hydrochloride (1-15 mg/kg; p.o.) is fully protective in a causal prophylactic mouse model of malaria
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Mice (causal prophylactic rodent malaria model) [1] |
| Dosage: | 1-15 mg/kg |
| Administration: | P.o. |
| Result: | A single oral dose of 10 mg of KAF156/kg administered 2 h before infection was fully protective. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT04072302 | Novartis Pharmaceuticals|Novartis |
Malaria
|
September 15, 2014 | Phase 1 |
| NCT05330273 | Novartis Pharmaceuticals|Medicines for Malaria Venture|Novartis |
Malaria
|
April 28, 2022 | Phase 1 |
| NCT05236530 | Novartis Pharmaceuticals|Medicines for Malaria Venture|Novartis |
Malaria
|
March 9, 2022 | Phase 1 |
| NCT03167242 | Novartis Pharmaceuticals|Medicines for Malaria Venture|Novartis |
Acute Uncomplicated Plasmodium Falciparum Malaria
|
August 2, 2017 | Phase 2 |
| NCT05084651 | Novartis Pharmaceuticals|Medicines for Malaria Venture|Novartis |
Malaria
|
November 18, 2021 | Phase 1 |
| NCT01753323 | Novartis Pharmaceuticals|Novartis |
Malaria
|
March 2013 | Phase 2 |
| NCT04546633 | Novartis Pharmaceuticals|European and Developing Countries Clinical Trials Partnership (EDCTP)|Novartis |
Uncomplicated Plasmodium Falciparum Malaria
|
February 16, 2021 | Phase 2 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvent & Solubility
DMSO : 100 mg/mL ( 223.26 mM ; Need ultrasonic)
H 2 O : 33.33 mg/mL ( 74.41 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.2326 mL | 11.1630 mL | 22.3259 mL |
| 5 mM | 0.4465 mL | 2.2326 mL | 4.4652 mL |
| 10 mM | 0.2233 mL | 1.1163 mL | 2.2326 mL |
References
- [1] Kuhen KL, et al. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrob Agents Chemother. 2014;58(9):5060-5067.
- [2] Leong FJ, et al. A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrob Agents Chemother. 2014;58(11):6437-6443.
