| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
FLT3 (wild-type and mutant forms). PHI-101 is a dual inhibitor of FLT3 and CHK2, with potent activity against FLT3 single activating mutations (ITD or TKD) as well as double (ITD/D835Y or ITD/F691L) and triple (ITD/D835Y/F691L) resistance mutations.
|
|---|---|
| ln Vitro |
PHI-101 is active against a number of FLT3/ITD resistance mutations including FLT3/ITD/A627T, FLT3/ITD/N676D, and FLT3/ITD/F691L, with IC50s of 0.1 nM, 2.3 nM, and 14.6 nM, respectively. It also has a high off-rate for FLT3 inhibition (t1/2 off ~3.1 hours), distinguishing it from other Type II inhibitors.
|
| ln Vivo |
PHI-101 is an orally active FLT3 inhibitor that effectively overcomes resistance associated with numerous drug-resistant mutations. It is currently in clinical development for AML. In preclinical models, it demonstrates robust anti-tumor activity against FLT3-mutant AML, including those resistant to first-generation FLT3 inhibitors. Phase 1/2 clinical trials are ongoing.
|
| Enzyme Assay |
Cell-free FLT3 kinase assays are performed using recombinant wild-type and mutant FLT3 enzymes. The compound is incubated with the enzyme and a peptide substrate in the presence of ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit. IC50 values against various FLT3 mutants are calculated from dose-response curves.
|
| Cell Assay |
FLT3-mutant human AML cell lines (e.g., MV4-11, MOLM-13) are seeded in 96-well plates and treated with increasing concentrations of PHI-101 for 72 hours. Cell viability is assessed using the MTT assay or CellTiter-Glo reagent. The effect on FLT3 phosphorylation and downstream signaling (p-STAT5, p-ERK) is measured by Western blotting. IC50 values for cell proliferation are determined.
|
| Animal Protocol |
For in vivo efficacy studies, PHI-101 is administered orally to mice bearing FLT3-mutant AML xenografts (e.g., MV4-11). Dosing schedules are typically once daily for 2-4 weeks. Tumor volumes are measured with calipers. At study termination, tumors are excised for pharmacodynamic analysis of FLT3 phosphorylation and downstream signaling. Pharmacokinetic sampling is performed for PK/PD analysis.
|
| ADME/Pharmacokinetics |
PHI-101 is an orally active FLT3 inhibitor with favorable ADME properties. It has a high off-rate for FLT3 inhibition (t1/2 off ~3.1 hours), which may contribute to its ability to overcome resistance. PK parameters in preclinical species have been characterized to support its clinical development, but detailed data are proprietary.
|
| Toxicity/Toxicokinetics |
Preclinical toxicology studies have been conducted to support clinical development. The compound has generally been well-tolerated in Phase 1 clinical trials, with a manageable safety profile. Comprehensive toxicological data are not publicly detailed, but the compound has advanced to clinical studies, indicating acceptable preclinical safety.
|
| References | |
| Additional Infomation |
PHI-101, a Chk2 inhibitor, is an orally bioavailable checkpoint kinase 2 (chk2) inhibitor with potential antitumor and chemotherapy-enhancing activities. After oral administration, PHI-101 binds to and inhibits chk2, thereby preventing DNA damage repair caused by DNA-damaging agents. This may lead to tumor cell apoptosis and enhance the antitumor efficacy of various chemotherapeutic drugs. Chk2 is an ATP-dependent serine/threonine kinase and a key component of the DNA replication monitoring checkpoint system, which can be activated by double-strand breaks (DSBs); activated chk2 overexpression is present in various cancer cell types.
Other information: PHI-101 (Lasnotinib, CAS 2127107-15-5) is a next-generation FLT3 inhibitor in clinical development for acute myeloid leukemia (AML). It is designed to overcome resistance mutations that limit the efficacy of first-generation FLT3 inhibitors. Phase 1/2 clinical trials are ongoing. Not yet FDA-approved. |
| Molecular Formula |
C19H19FN4O2S
|
|---|---|
| Molecular Weight |
386.443166017532
|
| Exact Mass |
386.121
|
| CAS # |
2127107-15-5
|
| PubChem CID |
130358571
|
| Appearance |
White to yellow solid powder
|
| LogP |
2.6
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
27
|
| Complexity |
619
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C1C[C@@H](CNC1)NC(=O)C2=C(C=C(S2)C#CC3=CC(=CC=C3)F)NC(=O)N
|
| InChi Key |
ULVAGWVTXBTFRN-AWEZNQCLSA-N
|
| InChi Code |
InChI=1S/C19H19FN4O2S/c20-13-4-1-3-12(9-13)6-7-15-10-16(24-19(21)26)17(27-15)18(25)23-14-5-2-8-22-11-14/h1,3-4,9-10,14,22H,2,5,8,11H2,(H,23,25)(H3,21,24,26)/t14-/m0/s1
|
| Chemical Name |
3-(carbamoylamino)-5-[2-(3-fluorophenyl)ethynyl]-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5877 mL | 12.9386 mL | 25.8772 mL | |
| 5 mM | 0.5175 mL | 2.5877 mL | 5.1754 mL | |
| 10 mM | 0.2588 mL | 1.2939 mL | 2.5877 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04678102
Conditions:Platinum-resistant Ovarian Cancer|Platinum-refractory Ovarian Carcinoma|Platinum-Resistant Fallopian Tube Carcinoma|Platinum-Resistant Primary Peritoneal CarcinomaLink: https://clinicaltrials.gov/ct2/show/NCT04842370
Conditions:Relapsed or Refractory Acute Myeloid LeukemiaProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
