Drug (ID: DG01628) and It's Reported Resistant Information
Name
LY3009120
Synonyms
LY3009120; 1454682-72-4; LY-3009120; DP-4978; UNII-1GDT36RARO; LY 3009120; 1GDT36RARO; DP 4978; 1-(3,3-dimethylbutyl)-3-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea; CHEMBL3577124; 1-(3,3-Dimethylbutyl)-3-{2-Fluoro-4-Methyl-5-[7-Methyl-2-(Methylamino)pyrido[2,3-D]pyrimidin-6-Yl]phenyl}urea; 1-(3,3-Dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido(2,3-d)pyrimidin-6-yl)phenyl)urea; N-(3,3-Dimethylbutyl)-N'-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]urea; Urea, N-(3,3-dimethylbutyl)-N'-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido(2,3-d)pyrimidin-6-yl)phenyl)-; 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl)phenyl)urea; Urea, N-(3,3-dimethylbutyl)-N'-[2-fluoro-4-methyl-5-[7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl]phenyl]-; GTPL8943; SCHEMBL15241297; CHEBI:167662; BCP23869; EX-A1638; BDBM50096279; DP4978; NSC781761; NSC801010; s7842; ZINC205861291; CCG-268937; NSC-781761; NSC-801010; SB16924; NCGC00481604-01; AC-30240; AS-74984; HY-12558; QC-11801; DP-4978;LY-3009120; J3.580.324F; C72761; Q27082823; B2693-470864; 1-(2-Fluoro-4-methyl-5-(2-methylamino-7-methylpyrido[2,3-d]pyrimidine-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea; 3-(3,3-DIMETHYLBUTYL)-1-{2-FLUORO-4-METHYL-5-[7-METHYL-2-(METHYLAMINO)PYRIDO[2,3-D]PYRIMIDIN-6-YL]PHENYL}UREA; 4Z5
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Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Phase 3
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Melanoma [ICD-11: 2C30]
[2]
Target Serine/threonine-protein kinase Raf (RAF) ARAF_HUMAN ;
BRAF_HUMAN ;
RAF1_HUMAN
[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
6
IsoSMILES
CC1=CC(=C(C=C1C2=C(N=C3C(=C2)C=NC(=N3)NC)C)NC(=O)NCCC(C)(C)C)F
InChI
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)
InChIKey
HHCBMISMPSAZBF-UHFFFAOYSA-N
PubChem CID
71721540
Type(s) of Resistant Mechanism of This Drug
  ADTT: Aberration of the Drug's Therapeutic Target
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Molecule Alteration IF-deletion
p.L485_P490delLNVTAP (c.1453_1470del18)
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Hematologic cancer [ICD-11: 2B3Z]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Molecule Alteration Missense mutation
p.K601N (c.1803A>C)
Sensitive Disease Hematologic Cancer [ICD-11: MG24.Y]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Pancreatic cancer [ICD-11: 2C10]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Molecule Alteration Complex-indel
p.V487_P492delinsA (c.1460_1474del15)
Sensitive Disease Pancreatic ductal adenocarcinoma [ICD-11: 2C10.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Lung cancer [ICD-11: 2C25]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Aberration of the Drug's Therapeutic Target (ADTT) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Molecule Alteration Complex-indel
p.L485_P490delinsY (c.1453_1470delinsTAT)
Sensitive Disease Lung adenocarcinoma [ICD-11: 2C25.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
Melanoma [ICD-11: 2C30]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: GTPase Nras (NRAS) [2]
Molecule Alteration Missense mutation
p.Q61L (c.182A>T)
Resistant Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance
CellTiter-Glo assay; Enzymatic kinase assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]
Molecule Alteration Missense mutation
p.L597S (c.1789_1790delCTinsTC)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation MAPK signaling pathway Inhibition hsa04010
In Vitro Model Skin sample N.A.
In Vivo Model Mouse PDX model Mus musculus
Experiment for
Drug Resistance
Crystal violet staining assay
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]
Molecule Alteration Missense mutation
p.V600E (c.1799T>A)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance
CellTiter-Glo assay; Enzymatic kinase assay
Key Molecule: GTPase Nras (NRAS) [2]
Molecule Alteration Missense mutation
p.Q61K (c.181C>A)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance
CellTiter-Glo assay; Enzymatic kinase assay
Key Molecule: GTPase Nras (NRAS) [2]
Molecule Alteration Missense mutation
p.G13D (c.38G>A)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance
CellTiter-Glo assay; Enzymatic kinase assay
Key Molecule: Cellular tumor antigen p53 (TP53) [2]
Molecule Alteration Missense mutation
p.D259Y (c.775G>T)
Sensitive Disease Melanoma [ICD-11: 2C30.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model A375 cells Skin Homo sapiens (Human) CVCL_0132
Sk-Mel28 cells Skin Homo sapiens (Human) CVCL_0526
A2058 cells Skin Homo sapiens (Human) CVCL_1059
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
A375 cells Skin Homo sapiens (Human) CVCL_0132
WM2664 cells Skin Homo sapiens (Human) CVCL_2765
SkMEL 30 cells Skin Homo sapiens (Human) CVCL_0039
SkMEL 2 cells Skin Homo sapiens (Human) CVCL_0069
SH4 cells Skin Mus musculus (Mouse) CVCL_7702
MEXF-535 cells Skin Homo sapiens (Human) N.A.
MEXF-1792 cells Skin Homo sapiens (Human) N.A.
MEXF-1341 cells Skin Homo sapiens (Human) N.A.
M14 cells Hypodermis Homo sapiens (Human) CVCL_1395
GAK cells Lnguinal lymph node Homo sapiens (Human) CVCL_1225
Colo829 cells Skin Homo sapiens (Human) CVCL_1137
In Vivo Model Female NIH nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blotting analysis; Crystallization assay; X-ray data collection and structure determination assay
Experiment for
Drug Resistance
CellTiter-Glo assay; Enzymatic kinase assay
Ovarian cancer [ICD-11: 2C73]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]
Molecule Alteration IF-deletion
p.N486_P490delNVTAP (c.1457_1471del15)
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
NIH 3T3 cells Colon Homo sapiens (Human) CVCL_0594
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
OV-90 cells Ascites Homo sapiens (Human) CVCL_3768
H2405 cells Lung Homo sapiens (Human) CVCL_1551
In Vivo Model NIH nude rat xenograft model Rattus norvegicus
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CellTiter-Glo assay; Colony transformation assay; Cell-cycle analysis; BrdUrd incorporation assay
References
Ref 1 Dual MAPK Inhibition Is an Effective Therapeutic Strategy for a Subset of Class II BRAF Mutant MelanomasClin Cancer Res. 2018 Dec 15;24(24):6483-6494. doi: 10.1158/1078-0432.CCR-17-3384. Epub 2018 Jun 14.
Ref 2 Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant CancersCancer Cell. 2015 Sep 14;28(3):384-98. doi: 10.1016/j.ccell.2015.08.002. Epub 2015 Sep 3.
Ref 3 Oncogenic BRAF Deletions That Function as Homodimers and Are Sensitive to Inhibition by RAF Dimer Inhibitor LY3009120Cancer Discov. 2016 Mar;6(3):300-15. doi: 10.1158/2159-8290.CD-15-0896. Epub 2016 Jan 5.

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