LY-3009120

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H29FN6O
Molecular Weight	424.5144
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC1=NC2=NC(C)=C(C=C2C=N1)C3=CC(NC(=O)NCCC(C)(C)C)=C(F)C=C3C

InChI

InChIKey=HHCBMISMPSAZBF-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C23H29FN6O
Molecular Weight	424.5144
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02014116 | https://www.ncbi.nlm.nih.gov/pubmed/27999210 | https://encrypted.google.com/patents/WO2013134243A1

LY-3009120 is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf, and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor LY3009120 inhibits Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. LY3009120 is being investigated in phase I clinical trial.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase B-raf 21 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804	Inhibitor 8504	15.0 nM [IC50]
Serine/threonine-protein kinase RAF 11 Target ID: CHEMBL1906 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804	Inhibitor 8504	4.3 nM [IC50]
Ephrin type-A receptor 2 8 Target ID: CHEMBL2068 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804	Inhibitor 8504	20.0 nM [IC50]
Serine/threonine-protein kinase A-Raf 3 Target ID: CHEMBL1169596 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804	Inhibitor 8504	44.0 nM [IC50]
Mixed lineage kinase 7 1 Target ID: CHEMBL3886 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25965804	Inhibitor 8504	39.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Melanoma 88 Sources: https://clinicaltrials.gov/ct2/show/NCT02014116	Primary	Phase I 438	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: https://clinicaltrials.gov/ct2/show/NCT02014116	Primary	Phase I 438	Unknown Approved Use Unknown
Colorectal cancer 102 Sources: https://clinicaltrials.gov/ct2/show/NCT02014116	Primary	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
105.29 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
420.3 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
436 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
515 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
675 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
704.74 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
976 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1430 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
688 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
775 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1717.76 ng/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
821 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31645440/	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY-3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
960 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	50 mg 2 times / day multiple, oral dose: 50 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2240 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2360 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3520 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	100 mg 2 times / day steady-state, oral dose: 100 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4640 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5140 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7560 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8460 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5910 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	400 mg 2 times / day multiple, oral dose: 400 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5440 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	400 mg 2 times / day steady-state, oral dose: 400 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
16400 ng × h/mL CLINICAL TRIAL https://classic.clinicaltrials.gov/ct2/show/results/NCT02014116	500 mg 2 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8983 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31645440/	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	LY-3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.73 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31645440/	300 mg 2 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:		LY-3009120 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	DLT: Pain, Stomatitis... Dose limiting toxicities: Pain (grade 3, 50%) Stomatitis (grade 3, 50%) Arthralgia (grade 3, 50%) Myalgia (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
300 mg 2 times / day multiple, oral RP2D Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	DLT: Blurred vision, Dermatitis acneiform... Disc. AE: Myalgia... Dose limiting toxicities: Blurred vision (grade 2, 6.25%) Dermatitis acneiform (grade 2, 6.25%) AEs leading to discontinuation/dose reduction: Myalgia (6.25%) Sources: https://pubmed.ncbi.nlm.nih.gov/31645440

AEs

AE	Significance	Dose	Population
Arthralgia	grade 3, 50% DLT, Disc. AE	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Myalgia	grade 3, 50% DLT, Disc. AE	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Pain	grade 3, 50% DLT, Disc. AE	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Stomatitis	grade 3, 50% DLT, Disc. AE	500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Myalgia	6.25% Disc. AE	300 mg 2 times / day multiple, oral RP2D Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Blurred vision	grade 2, 6.25% DLT	300 mg 2 times / day multiple, oral RP2D Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440
Dermatitis acneiform	grade 2, 6.25% DLT	300 mg 2 times / day multiple, oral RP2D Dose: 300 mg, 2 times / day Route: oral Route: multiple Dose: 300 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31645440	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/31645440

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001DII	https://www.1pchem.com/search?query=1P001DII
AChemBlock	H-8969	http://www.achemblock.com/catalogsearch/result/?q=H-8969
Angene	AGN-PC-0WHAC3	http://www.angenechemical.com/productshow/AGN-PC-0WHAC3.html
ApexBio Technology	A8716	https://www.apexbt.com/catalogsearch/result/?q=A8716
AstaTech	C72761	http://astatechinc.com/CPSResult.php?CRNO=C72761
BLD Pharm	BD303416	http://www.bldpharm.com/search/Search.html?keyword=BD303416
Cayman Chemical	21504	http://www.caymanchem.com/app/template/Product.vm/catalog/21504
Chem Scene	CS-4147	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-4147
ChemShuttle	140522	https://www.chemshuttle.com/catalogsearch/result/?q=140522
eMolecules	53744842	https://orderbb.emolecules.com/search/#?query=53744842
Excenen	EX-A1638	http://www.excenen.com/searchresultlist.php?id=EX-A1638
KeyOrganics	AS-74984	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74984
mcule	MCULE-7282033383	https://mcule.com/MCULE-7282033383/
MedChem Express	HY-12558	https://www.medchemexpress.com/search.html?q=HY-12558&ft=&fa=&fp=
Molnova	M11963	https://www.molnova.com/en/serch-list.html?keywords=M11963
MolPort	MolPort-039-137-278	https://www.molport.com/shop/molecule-link/MolPort-039-137-278
MuseChem	I001758	https://www.musechem.com/product/I001758.html
Selleck Chemicals	S7842	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7842
ShangHai Biochempartner	BCP23869	http://www.biochempartner.com/search_BCP23869
TargetMol	T6882	https://www.targetmol.com/search?keyword=T6882

PubMed

Title	Date	PubMed
Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers.	2015-09-14	26343583

Patents

Sample Use Guides

In Vivo Use Guide

LY3009120 in escalating dose cohorts given orally BID (twice daily) every 12 hours for a 28-day cycle

Route of Administration: Oral

In Vitro Use Guide

A375 cells (catalog no. CRL-1619) were obtained from the American Type Culture Collection (ATCC, Manassas, VA). Cells were grown in DMEM high glucose supplemented with 10% characterized fetal bovine serum (Invitrogen, Carlsbad, CA) and 1% penicillin/streptomycin/L-glutamine at 37 °C, 5% CO2, and 95% humidity. Cells were allowed to expand until 70−95% confluency at which point they were subcultured or harvested for assay use. A serial dilution of test compound (LY-3009120) was dispensed into a 384-well black clear bottom plate in triplicate. Six-hundred-twenty-five cells were added per well in 50 μL of complete growth medium in the 384-well plate. Plates were incubated for 67 h at 37 °C, 5% CO2, and 95% humidity. At the end of the incubation period, 10 μL of a 440 μM solution of resazurin (Sigma, St. Louis, MO) in PBS was added to each well of the plate and plates were incubated for an additional 5 h at 37 °C, 5% CO2, and 95% humidity. Plates were read on a Synergy2 reader (Biotek, Winooski, VT) using an excitation of 540 nm and an emission of 600 nm.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:43:01 GMT 2025` Edited by `admin` on `Mon Mar 31 20:43:01 GMT 2025`
Record UNII	1GDT36RARO
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DP-4978

Preferred Name

English

LY-3009120

Common Name

English

UREA, N-(3,3-DIMETHYLBUTYL)-N'-(2-FLUORO-4-METHYL-5-(7-METHYL-2-(METHYLAMINO)PYRIDO(2,3-D)PYRIMIDIN-6-YL)PHENYL)-

Systematic Name

English

LY3009120

Code

English

PAN-RAF INHIBITOR LY3009120

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2336