| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
Purity: ≥98%
Rineterkib (LTT-462; ERK-IN-1; ERK-IN1), the compound B extracted from WO2018051306A1, is a novel and potent RAF and ERK1/2 inhibitor with anticancer activity. It has the potential to treat a proliferative disease marked by mutations that activate the MAPK pathway. The focus of the activity is on the treatment of KRAS-mutant non-small cell lung cancer (NSCLC), BRAF-mutant NSCLC, KRAS-mutant pancreatic cancer, KRAS-mutant colorectal cancer (CRC), and KRAS-mutant ovarian cancer.
| Targets |
RAF; ERK1; ERK2
RAF and ERK1/2 inhibitor [2] |
|---|---|
| ln Vitro |
Rineterkib demonstrated preclinical activity in multiple MAPK-activated cancer cell lines and xenograft models [2]
|
| ln Vivo |
ERK-IN-1 (compound B) (50, 75 mg/kg, p.o., qd/q2d, 27 days), in the Calu-6 human NSCLC subcutaneous tumor xenograft model in mice, treatment significantly reduces the tumor volume.
Rineterkib showed preclinical activity in multiple MAPK-activated xenograft models [2] |
| Animal Protocol |
Calu-6 NSCLC xenograft tumor models in mice[1].
50, 75 mg/kg. Orally either daily (qd) or every other day (q2d) for 27 days. |
| References | |
| Additional Infomation |
Rineterkib is an extracellular signal-regulated kinase (ERK) inhibitor currently being investigated in NCT04097821 (a randomized, open-label, phase I/II open-platform study evaluating the safety and efficacy of a novel ruxolitinib combination therapy in patients with myelofibrosis). Rineterkib is an orally potent ERK inhibitor with potential antitumor activity. After oral administration, rinterkib binds to ERK and inhibits its activity, thereby preventing the activation of ERK-mediated signal transduction pathways. This ultimately leads to the suppression of ERK-dependent tumor cell proliferation and survival. The mitogen-activated protein kinase (MAPK)/ERK pathway is upregulated in various tumor cell types and plays a crucial role in tumor cell proliferation, differentiation, and survival.
Rineterkib Also known as LTT-462 or ERK-IN-1 [2] In a phase I dose-finding study (NCT02711345), Rineterkib was used as a monotherapy in adult patients with advanced cancers including ovarian tumors, non-small cell lung cancer, and melanoma. The results showed that it was well tolerated, but its clinical activity was limited [2] Currently, phase Ib and phase II clinical trials are underway to explore the efficacy of LTT462 in combination with RAF inhibitors (LXH254) for the treatment of non-small cell lung cancer and melanoma (NCT02974725 and NCT04417621) [2] A phase Ib trial is exploring the effects of LTT462 in combination with different RAF inhibitors. Efficacy of combination therapy with inhibitors in colorectal cancer (NCT04294160) [2] A multi-arm clinical trial is exploring the efficacy of LTT462 in combination with the JAK inhibitor (ruxotinib) [2] |
| Molecular Formula |
C26H27BRF3N5O2
|
|---|---|
| Molecular Weight |
578.4241
|
| Exact Mass |
577.13
|
| Elemental Analysis |
C, 53.99; H, 4.71; Br, 13.81; F, 9.85; N, 12.11; O, 5.53
|
| CAS # |
1715025-32-3
|
| Related CAS # |
Rineterkib hydrochloride;1715025-34-5
|
| PubChem CID |
118045847
|
| Appearance |
White to light yellow solid powder
|
| LogP |
3.1
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
37
|
| Complexity |
757
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CNC[C@H](C1=CC(=CC(=C1)Br)F)NC(=O)C2=C(C=C(C=C2)C3=NC(=CN=C3N)[C@H]4CC[C@@H]([C@H](C4)F)O)F
|
| InChi Key |
YFCIFWOJYYFDQP-PTWZRHHISA-N
|
| InChi Code |
InChI=1S/C26H27BrF3N5O2/c1-32-11-21(15-6-16(27)10-17(28)7-15)35-26(37)18-4-2-14(9-19(18)29)24-25(31)33-12-22(34-24)13-3-5-23(36)20(30)8-13/h2,4,6-7,9-10,12-13,20-21,23,32,36H,3,5,8,11H2,1H3,(H2,31,33)(H,35,37)/t13-,20-,21+,23-/m0/s1
|
| Chemical Name |
4-[3-amino-6-[(1S,3S,4S)-3-fluoro-4-hydroxycyclohexyl]pyrazin-2-yl]-N-[(1S)-1-(3-bromo-5-fluorophenyl)-2-(methylamino)ethyl]-2-fluorobenzamide
|
| Synonyms |
ERK-IN 1; ERK IN-1; ERK-IN-1
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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: ~200 mg/mL (~345.8 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.64 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (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 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7288 mL | 8.6442 mL | 17.2885 mL | |
| 5 mM | 0.3458 mL | 1.7288 mL | 3.4577 mL | |
| 10 mM | 0.1729 mL | 0.8644 mL | 1.7288 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 |
| NCT04097821 | Active Recruiting |
Drug: NIS793 Drug: Rineterkib |
Myelofibrosis | Novartis Pharmaceuticals | September 26, 2019 | Phase 1 Phase 2 |
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