| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
Purity: ≥98%
IPN-60090 ( IACS-6274; IPN60090) is a novel, potent, orally bioavailable, and selective inhibitor of GLS1, or kidney-type glutaminase, a crucial enzyme for the synthesis of metabolic energy. It is possible to use IPN-60090 in GLS1-mediated disease research. It may also have immunostimulating/immunomodulating and anticancer properties. Human glutaminase is an enzyme that is necessary for the conversion of the amino acid glutamine into glutamate. IPN60090 specifically targets, binds to, and inhibits this enzyme.
| Targets |
GLS1 (IC50 = 31 nM)
|
|---|---|
| ln Vitro |
GLS-1, also known as kidney-type or KGA, and GLS-2, also known as liver-type or LGA, are the two known isoforms of glutaminase. GLS-2 expression seems to be mostly restricted to the liver, whereas GLS-1 is widely expressed.
IPN60090 has no effect against GLS-2, with an IC50 of >50000 nM, and inhibits purified recombinant human GLS-1 (GAC isoform) with an IC50 of 31 nM in a dual-coupled enzyme assay[2].
IPN60090 has an IC50 of 26 nM and prevents A549 cell proliferation[2].
|
| ln Vivo |
IPN60090 (3 mg/kg for i.v.; 10 mg/kg for p.o.) exhibits exceptional pharmacokinetic characteristics, including CL=4.1 mL/min/kg, t1/₂=1 hour, Cmax=19 μM, and F%=89%[2]. IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days) exhibits comparable effectiveness and engagement with the target as CB-839 when taken orally at a dose of 250 mg/kg twice a day. Furthermore, for the upcoming model study, the tolerated dose of IPN-60090 is 100 mg/kg BID[2]. IPN-60090 (oral administration; 100 mg/kg; twice daily; 30 days; monotherapy or in combination with TAK228 ) inhibits the growth of tumors. In a dose-dependent manner, IPN-60090 exhibits strong in vivo target engagement on its own. Day 4 and Day 28 show lower glutamate/glutamine ratios and free plasma concentrations of IPN-60090 at 4 hours post-dose[2]. Additionally, IPN-60090 alone results in a 28% in vivo tumor growth inhibition, whereas IPN-60090 in combination with TAK228 strongly causes an 85% tumor growth inhibition[2].
|
| Animal Protocol |
Female CD-1 mice[2]
3 mg/kg for i.v.; 10 mg/kg for p.o. (Pharmacokinetic Analysis) Intravenous injection and oral administration |
| References |
| Molecular Formula |
C₂₄H₂₇F₃N₈O₃
|
|---|---|
| Molecular Weight |
532.518194437027
|
| Exact Mass |
532.22
|
| Elemental Analysis |
C, 54.13; H, 5.11; F, 10.70; N, 21.04; O, 9.01
|
| CAS # |
1853164-83-6
|
| Related CAS # |
IPN60090 dihydrochloride;2102101-72-2
|
| Appearance |
Solid powder
|
| SMILES |
CC1=CC(=CC(=N1)CC(=O)NC2=NN=C(C=C2)CC[C@H](CN3C=C(N=N3)C(=O)NC)F)OC4CC(C4)(F)F
|
| InChi Key |
GEHZIZWHNLQFAS-OAHLLOKOSA-N
|
| InChi Code |
InChI=1S/C24H27F3N8O3/c1-14-7-18(38-19-10-24(26,27)11-19)8-17(29-14)9-22(36)30-21-6-5-16(31-33-21)4-3-15(25)12-35-13-20(32-34-35)23(37)28-2/h5-8,13,15,19H,3-4,9-12H2,1-2H3,(H,28,37)(H,30,33,36)/t15-/m1/s1
|
| Chemical Name |
1-[(2R)-4-[6-[[2-[4-(3,3-difluorocyclobutyl)oxy-6-methylpyridin-2-yl]acetyl]amino]pyridazin-3-yl]-2-fluorobutyl]-N-methyltriazole-4-carboxamide
|
| Synonyms |
IACS-6274; IACS6274; IACS 6274; IPN60090; IPN 60090; IPN-60090
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 5~31.4 mg/mL (9.4~59.0 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.14 mg/mL (5.90 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 31.4 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8779 mL | 9.3893 mL | 18.7786 mL | |
| 5 mM | 0.3756 mL | 1.8779 mL | 3.7557 mL | |
| 10 mM | 0.1878 mL | 0.9389 mL | 1.8779 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03894540 | Terminated | Drug: IPN60090 Drug: pembrolizumab |
Solid Tumor | Ipsen | March 22, 2019 | Phase 1 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA