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MedKoo Cat#: 206161 | Name: LY3009120
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

LY3009120, also known as DP-4978, is potent and selective pan-RAF inhibitor with potential anticancer activity. LY3009120 showed activities against BRaf or Ras mutant tumor cells . LY3009120 binds to ARaf, BRaf and CRaf isoforms with similar affinity in cells with activating mutations of BRaf or KRas. LY3009120 induces minimal paradoxical pathway activation in NRas or KRas mutant cells. LY3009120 inhibits MEK phosphorylation and cell proliferation in vitro, and exhibits anti-tumor activity in multiple xenograft models carrying mutations in BRaf, NRas or KRas.

Chemical Structure

LY3009120
LY3009120
CAS#1454682-72-4

Theoretical Analysis

MedKoo Cat#: 206161

Name: LY3009120

CAS#: 1454682-72-4

Chemical Formula: C23H29FN6O

Exact Mass: 424.2387

Molecular Weight: 424.52

Elemental Analysis: C, 65.07; H, 6.89; F, 4.48; N, 19.80; O, 3.77

Price and Availability

Size Price Availability Quantity
10mg USD 110.00 Ready to ship
25mg USD 210.00 Ready to ship
50mg USD 350.00 Ready to ship
100mg USD 600.00 Ready to ship
200mg USD 1,050.00 Ready to ship
500mg USD 2,350.00 Ready to ship
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Related CAS #
No Data
Synonym
LY3009120; LY-3009120; LY 3009120; DP4978; DP 4978; DP-4978.
IUPAC/Chemical Name
1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea
InChi Key
HHCBMISMPSAZBF-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H29FN6O/c1-13-9-18(24)19(29-22(31)26-8-7-23(3,4)5)11-16(13)17-10-15-12-27-21(25-6)30-20(15)28-14(17)2/h9-12H,7-8H2,1-6H3,(H2,26,29,31)(H,25,27,28,30)
SMILES Code
O=C(NC1=CC(C2=CC3=CN=C(NC)N=C3N=C2C)=C(C)C=C1F)NCCC(C)(C)C
Appearance
Light yellow 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, not in water
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
  LY3009120 is a potentially best-in-class inhibitor of three Raf isoforms and Raf dimer, with activity against tumor cells with BRaf, NRas or KRas mutations, as well as melanoma cells with acquired resistance to current BRaf therapies.    
Biological target:
LY03009120 (DP-4978) is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively.
In vitro activity:
The effects of LY3009120 on a panel of CRC cell lines based on BRAFmut and KRASmut background were assessed. Biochemical assay data demonstrated inhibition of BRAFV600E, BRAFWT and CRAFWT with IC50 values of 5.8, 9.1 and 15 nM respectively. In the whole-cell based KiNativ assay measuring the affinity of LY3009120 to each RAF isoform, the IC50 was similar among the three RAF isoforms, specifically, 44, 31-47 and 42 nM for ARAF, BRAF and CRAF respectively. Based on the biochemical and KiNativ assay results, the anti-proliferative effects of LY3009120 using concentrations of low nM up to 10 μM were examined. The anti-proliferative effects of LY3009120 assayed by CellTiter Glo (CTG) and EC50 values were plotted according to the mutational status of each cell line. Cell lines harboring BRAFV600E mutations were the most sensitive to LY3009120, followed by cell lines harboring KRASG13 and KRASG12 mutations (Figure 1A). There was a >5-fold difference between the most sensitive lines (BRAFmut and KRASmut) and the least sensitive lines (KRASWT/BRAFWT) (Figure 1A). Of note, sensitivity of CRC cell lines to LY3009120 could not be predicted based on the activation status of the MAPK and PI3K signaling cascades, but rather appeared to be a function of the BRAF and KRAS mutational status (Figure 1A and 1C). For example, the cell line SW480 (KRASmut) was slightly less responsive to LY3009120 than LoVo (KRASmut) despite SW480 exhibiting lower levels of pERK1/2 (Figure 1C). Reference: Oncotarget. 2017 Feb 7;8(6):9251-9266. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27999210/
In vivo activity:
The in vivo efficacy of LY3009120 was evaluated in CRC xenograft models of various mutational backgrounds. Treatment of Colo 205 xenografts (BRAFmut) with LY3009120 resulted in statistically significant tumor regression (46.7% regression from baseline, p < 0.001) (Figure 5A, top left panel), while treatment of HCT 116 xenografts (KRASmut) resulted in statistically significant inhibition of tumor growth (delta(T/C)= 35.4%, p < 0.01) (Figure 5A, top right panel). Examination of an additional BRAFmut xenograft model, HT-29, confirmed the in vivo efficacy of LY3009120 (delta(T/C)= 40%, p < 0.001) in a BRAFmut CRC setting (Figure 5A, lower left panel), while LY3009120-treatment of Colo 320HSR (KRASWT/BRAFWT) indicated lack of in vivo efficacy in a KRASWT/BRAFWT xenograft model (Figure5A, lower right panel). Reference: Oncotarget. 2017 Feb 7;8(6):9251-9266. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/27999210/
Solvent mg/mL mM
Solubility
DMSO 20.0 47.11
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 424.52 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:
In vitro protocol:
1. Vakana E, Pratt S, Blosser W, Dowless M, Simpson N, Yuan XJ, Jaken S, Manro J, Stephens J, Zhang Y, Huber L, Peng SB, Stancato LF. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266. doi: 10.18632/oncotarget.14002. PMID: 27999210; PMCID: PMC5354729. 2. Yang SM, Park YK, Kim JI, Lee YH, Lee TY, Jang BC. LY3009120, a pan-Raf kinase inhibitor, inhibits adipogenesis of 3T3-L1 cells by controlling the expression and phosphorylation of C/EBP-α, PPAR-γ, STAT‑3, FAS, ACC, perilipin A, and AMPK. Int J Mol Med. 2018 Dec;42(6):3477-3484. doi: 10.3892/ijmm.2018.3890. Epub 2018 Sep 21. PMID: 30272260.
In vivo protocol:
1. Vakana E, Pratt S, Blosser W, Dowless M, Simpson N, Yuan XJ, Jaken S, Manro J, Stephens J, Zhang Y, Huber L, Peng SB, Stancato LF. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer. Oncotarget. 2017 Feb 7;8(6):9251-9266. doi: 10.18632/oncotarget.14002. PMID: 27999210; PMCID: PMC5354729.