RAF709
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MedKoo CAT#: 406990

CAS#: 1628838-42-5

Description: RAF709 is a Raf kinase inhibitor.

Chemical Structure

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RAF709
CAS# 1628838-42-5
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406990
Name: RAF709
CAS#: 1628838-42-5
Chemical Formula: C28H29F3N4O4
Exact Mass: 542.21
Molecular Weight: 542.560
Elemental Analysis: C, 61.99; H, 5.39; F, 10.50; N, 10.33; O, 11.80

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
Bulk inquiry

Synonym: RAF709; RAF-709; RAF 709.

IUPAC/Chemical Name: N-(2-methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3-(trifluoromethyl)benzamide

InChi Key: FYNMINFUAIDIFL-UHFFFAOYSA-N

InChi Code: InChI=1S/C28H29F3N4O4/c1-18-24(15-22(17-32-18)34-26(36)19-3-2-4-21(13-19)28(29,30)31)20-14-25(35-7-11-38-12-8-35)27(33-16-20)39-23-5-9-37-10-6-23/h2-4,13-17,23H,5-12H2,1H3,(H,34,36)

SMILES Code: O=C(NC1=CN=C(C)C(C2=CC(N3CCOCC3)=C(OC4CCOCC4)N=C2)=C1)C5=CC(C(F)(F)F)=CC=C5

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: RAF709 is a potent, selective, and efficacious RAF inhibitor with IC50s of 0.4 nM and 0.5 nM for BRAF and CRAF, respectively.
In vitro activity: In in vitro biochemical assays, RAF709 exhibited potent inhibitory activity targeting BRAF, BRAFV600E, and CRAF with IC50 values ranging between 0.3 to 1.5 nmol/L (Fig. 1). Data obtained from the cocrystal structure of RAF709 in complex with the BRAF kinase domain revealed that the protein adopts an inactive conformation with the DFG out and the αC-helix in, characteristic of a type II inhibitor binding mode. In A375 (BRAFV600E) cells, both dabrafenib and RAF709 showed robust activity inhibiting mutant BRAF monomer–driven ERK activation with IC50s of 5 nmol/L and 44 nmol/L, respectively. In comparison, in HCT116 cells (KRASG13D) pretreated with encorafenib, RAF709 exhibited equipotent activity inhibiting RAF dimer–driven signaling with a pERK IC50 of 79 nmol/L, whereas dabrafenib showed approximately 100-fold higher IC50 of 3 μmol/L. The same experiment was carried out in SK-MEL-30 (NRASQ61K) cells with similar results: RAF709 had an IC50 of 0.139 μmol/L (3.2-fold shift) and dabrafenib had an IC50 of 3.7 μmol/L (>700-fold shift; Supplementary Fig. S2). These data suggest that RAF709 inhibits both RAF monomers and dimers with similar potency. Reference: Cancer Res. 2018 Mar 15; 78(6): 1537-1548. https://cancerres.aacrjournals.org/content/78/6/1537.long
In vivo activity: Nude mice bearing Calu-6 xenograft tumors were treated with a single dose of RAF709 across a wide dose range (from 10 to 200 mg/kg). Tumor tissues were then collected at multiple time points postdose to determine pMEK levels. As shown in Fig. 6A, RAF709 treatment led to inhibition of MEK phosphorylation in a dose-dependent manner both in degree and in duration. RAF709 at 100 mg/kg and 200 mg/kg was able to suppress pMEK to greater than 50% for more than 16 hours. In line with pMEK inhibition, RAF709 treatment resulted in dose-dependent antitumor activity starting from 30 mg/kg (Fig. 6B). Treatment with 30 mg/kg of RAF709 led to a 52% T/C, while treatment at 100 and 200 mg/kg resulted in tumor regressions of 47% and 88%, respectively, in line with the more durable pathway inhibition at the two higher dose levels. Reference: Cancer Res. 2018 Mar 15; 78(6): 1537-1548. https://cancerres.aacrjournals.org/content/78/6/1537.long

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 100.0 184.31
DMSO:PBS (pH 7.2) (1:2) 0.3 0.61
DMF 30.0 55.29
Ethanol 100.0 184.31

Preparing Stock Solutions

The following data is based on the product molecular weight 542.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF. Cancer Res. 2018 Mar 15;78(6):1537-1548. doi: 10.1158/0008-5472.CAN-17-2033. Epub 2018 Jan 17. PMID: 29343524.
In vitro protocol: 1. Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF. Cancer Res. 2018 Mar 15;78(6):1537-1548. doi: 10.1158/0008-5472.CAN-17-2033. Epub 2018 Jan 17. PMID: 29343524.
In vivo protocol: 1. Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF. Cancer Res. 2018 Mar 15;78(6):1537-1548. doi: 10.1158/0008-5472.CAN-17-2033. Epub 2018 Jan 17. PMID: 29343524.

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1. Shao W, Mishina YM, Feng Y, Caponigro G, Cooke VG, Rivera S, Wang Y, Shen F, Korn JM, Mathews Griner LA, Nishiguchi G, Rico A, Tellew J, Haling JR, Aversa R, Polyakov V, Zang R, Hekmat-Nejad M, Amiri P, Singh M, Keen N, Dillon MP, Lees E, Ramurthy S, Sellers WR, Stuart DD. Antitumor Properties of RAF709, a Highly Selective and Potent Inhibitor of RAF Kinase Dimers, in Tumors Driven by Mutant RAS or BRAF. Cancer Res. 2018 Mar 15;78(6):1537-1548. doi: 10.1158/0008-5472.CAN-17-2033. Epub 2018 Jan 17. PMID: 29343524.2
2. Maxson JE, Abel ML, Wang J, Deng X, Reckel S, Luty SB, Sun H, Gorenstein J,
Hughes SB, Bottomly D, Wilmot B, McWeeney SK, Radich J, Hantschel O, Middleton
RE, Gray NS, Druker BJ, Tyner JW. Identification and Characterization of Tyrosine
Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase
Inhibitor Screening and Genomic Analysis. Cancer Res. 2016 Jan 1;76(1):127-38.
doi: 10.1158/0008-5472.CAN-15-0817. PubMed PMID: 26677978; PubMed Central PMCID:
PMC4703549.