1. Braftovi
2. Lgx818
1. Lgx818
2. 1269440-17-6
3. Lgx-818
4. Braftovi
5. Encorafenib (lgx818)
6. Nvp-lgx818-nxa
7. Nvp-lgx-818-nxa
8. Nvp-lgx818
9. 8l7891mrb6
10. Methyl N-[(2s)-1-[[4-[3-[5-chloro-2-fluoro-3-(methanesulfonamido)phenyl]-1-propan-2-ylpyrazol-4-yl]pyrimidin-2-yl]amino]propan-2-yl]carbamate
11. Carbamic Acid, N-[(1s)-2-[[4-[3-[5-chloro-2-fluoro-3-[(methylsulfonyl)amino]phenyl]-1-(1-methylethyl)-1h-pyrazol-4-yl]-2-pyrimidinyl]amino]-1-methylethyl]-, Methyl Ester
12. Encorafenib [usan:inn]
13. Unii-8l7891mrb6
14. Lgx 818
15. Braftovi (tn)
16. Carbamic Acid, N-((1s)-2-((4-(3-(5-chloro-2-fluoro-3-((methylsulfonyl)amino)phenyl)-1-(1-methylethyl)-1h-pyrazol-4-yl)-2-pyrimidinyl)amino)-1-methylethyl)-, Methyl Ester
17. Encorafenib [mi]
18. Encorafenib(lgx-818)
19. Lgx-818(encorafenib)
20. Encorafenib [inn]
21. Encorafenib [jan]
22. Encorafenib [usan]
23. Encorafenib [who-dd]
24. Encorafenib (jan/usan/inn)
25. Gtpl7908
26. Schembl8228295
27. Chembl3301612
28. Dtxsid00155347
29. Encorafenib [orange Book]
30. Bdbm221688
31. Bcp08458
32. Ex-a1587
33. Mfcd25976758
34. Nsc778304
35. Nsc800093
36. S7108
37. Zinc68249103
38. Ccg-269960
39. Db11718
40. Nsc-778304
41. Nsc-800093
42. Ncgc00378599-03
43. Ac-30230
44. As-35201
45. Hy-15605
46. A13226
47. D11053
48. Us9314464, 9
49. Q15409405
50. (s)-methyl (1-((4-(3-(5-chloro-2-fluoro-3-(methylsulfonamido)phenyl)-1-isopropyl-1h-pyrazol-4-yl)pyrimidin-2-yl)amino)propan-2-yl)carbamate
51. Methyl N-((2s)-1-((4-(3-(5-chloro-2-fluoro-3-(methanesulfonamido)phenyl)(-1-(propan-2-yl)-1h-pyrazol-4-yl(pyrimidin-2-yl)amino)propan-2-yl)carbamate
52. Methyl N-[(2s)-1-({4-[3-(5-chloro-2-fluoro-3-methanesulfonamidophenyl)-1-(propan-2-yl)-1h-pyrazol-4-yl]pyrimidin-2-yl}amino)propan-2-yl]carbamate
| Molecular Weight | 540.0 g/mol |
|---|---|
| Molecular Formula | C22H27ClFN7O4S |
| XLogP3 | 2.7 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 10 |
| Exact Mass | 539.1517794 g/mol |
| Monoisotopic Mass | 539.1517794 g/mol |
| Topological Polar Surface Area | 149 Ų |
| Heavy Atom Count | 36 |
| Formal Charge | 0 |
| Complexity | 836 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 1 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
Used in combination with [Binimetinib] in metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.
Encorafenib is indicated:
- in combination with binimetinib is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation
- in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, who have received prior systemic therapy
Treatment of colorectal carcinoma
Treatment of melanoma
Encorafenib has shown improved efficacy in the treatment of metastatic melanoma. Encorafenib, a selective BRAF inhibitor (BRAFi), has a pharmacologic profile that is distinct from that of other clinically active BRAFis. Once-daily dosing of single-agent encorafenib has a distinct tolerability profile and shows varying antitumor activity across BRAFi-pretreated and BRAFi-nave patients with advanced/metastatic stage melanoma.
L01EC03
L - Antineoplastic and immunomodulating agents
L01 - Antineoplastic agents
L01E - Protein kinase inhibitors
L01EC - B-raf serine-threonine kinase (braf) inhibitors
L01EC03 - Encorafenib
Absorption
After oral administration, the median Tmax of encorafenib is 2 hours. At least 86% of the dose is absorbed. Administration of a single dose of BRAFTOVI 100 mg (0.2 times the recommended dose) with a high-fat, high-calorie meal (comprised of approximately 150 calories from protein, 350 calories from carbohydrates, and 500 calories from fat) decreased the mean maximum encorafenib concentration (Cmax) by 36% with no effect on AUC (area under the curve).
Route of Elimination
Following a single oral dose of 100 mg radiolabeled encorafenib, 47% (5% unchanged) of the administered dose was recovered in the feces and 47% (2% unchanged) was recovered in the urine.
Volume of Distribution
The blood-to-plasma concentration ratio is 0.58. The geometric mean (CV%) of apparent volume of distribution is 164 L (70%).
Clearance
The apparent clearance is 14 L/h (54%) at day 1, increasing to 32 L/h (59%) at steady-state.
The primary metabolic pathway is N-dealkylation, with CYP3A4 as the main contributor (83%) to total oxidative clearance of encorafenib in human liver microsomes, followed by CYP2C19 (16%) and CYP2D6 (1%).
The mean (CV%) terminal half-life (t1/2) of encorafenib is 3.5 hours (17%)
Encorafenib is a kinase inhibitor that specifically targets BRAF V600E, as well as wild-type BRAF and CRAF while tested with in vitro cell-free assays with IC50 values of 0.35, 0.47, and 0.3 nM, respectively. Mutations in the BRAF gene, including BRAF V600E, result in activated BRAF kinases that mahy stimulate tumor cell growth. Encorafenib is able to bind to other kinases in vitro including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36 and significantly reduce ligand binding to these kinases at clinically achievable concentrations ( 0.9 M). In efficacy studies, encorafenib inhibited the in vitro cell growth of tumor cell lines that express BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing the BRAF V600E mutation, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression. Encorafenib and binimetinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared with either drug alone, co-administration of encorafenib and binimetinib result in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. In addition to the above, the combination of encorafenib and binimetinib acted to delay the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared with the administration of either drug alone.
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