Drug Information

Drug (ID: DG01901) and It's Reported Resistant Information
Name
MM-151
Synonyms
MM-151
    Click to Show/Hide
Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Target Erbb3 tyrosine kinase receptor (Erbb-3) ERBB3_HUMAN [1]
Type(s) of Resistant Mechanism of This Drug
  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
Colorectal cancer [ICD-11: 2B91]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.S492R (c.1476C>G)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 3.20  Å
PDB: 3C09
Mutant Type Structure Method: X-ray diffraction Resolution: 2.80  Å
PDB: 6B3S
   Download The Information of Sequence       Download The Structure File   
RMSD: 0.58
TM score: 0.98774
Amino acid change:
S492R
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
-
L
L
E
E
E
E
310
|
K
K
K
K
V
V
C
C
N
N
G
G
I
I
G
G
I
I
G
G
320
|
E
E
F
F
K
K
D
D
S
S
L
L
S
S
I
I
N
N
A
A
330
|
T
T
N
N
I
I
K
K
H
H
F
F
K
K
N
N
C
C
T
T
340
|
S
S
I
I
S
S
G
G
D
D
L
L
H
H
I
I
L
L
P
P
350
|
V
V
A
A
F
F
R
R
G
G
D
D
S
S
F
F
T
T
H
H
360
|
T
T
P
P
P
P
L
L
D
D
P
P
Q
Q
E
E
L
L
D
D
370
|
I
I
L
L
K
K
T
T
V
V
K
K
E
E
I
I
T
T
G
G
380
|
F
F
L
L
L
L
I
I
Q
Q
A
A
W
W
P
P
E
E
N
N
390
|
R
R
T
T
D
D
L
L
H
H
A
A
F
F
E
E
N
N
L
L
400
|
E
E
I
I
I
I
R
R
G
G
R
R
T
T
K
K
Q
Q
H
H
410
|
G
G
Q
Q
F
F
S
S
L
L
A
A
V
V
V
V
S
S
L
L
420
|
N
N
I
I
T
T
S
S
L
L
G
G
L
L
R
R
S
S
L
L
430
|
K
K
E
E
I
I
S
S
D
D
G
G
D
D
V
V
I
I
I
I
440
|
S
S
G
G
N
N
K
K
N
N
L
L
C
C
Y
Y
A
A
N
N
450
|
T
T
I
I
N
N
W
W
K
K
K
K
L
L
F
F
G
G
T
T
460
|
S
S
G
G
Q
Q
K
K
T
T
K
K
I
I
I
I
S
R
N
N
470
|
R
R
G
G
E
E
N
N
S
S
C
C
K
K
A
A
T
T
G
G
480
|
Q
Q
V
V
C
C
H
H
A
A
L
L
C
C
S
S
P
P
E
E
490
|
G
G
C
C
W
W
G
G
P
P
E
E
P
P
R
R
D
D
C
C
500
|
V
V
S
S
C
C
R
R
N
N
V
V
S
S
R
R
G
G
R
R
510
|
E
E
C
C
V
V
D
D
K
K
H
H
H
H
H
H
H
H
H
H
520
|
H
H
Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.R451C (c.1351C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.S464L (c.1391C>T)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G465R (c.1393G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.G465E (c.1394G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.K467T (c.1400A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
Key Molecule: Epidermal growth factor receptor (EGFR) [1]
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Molecule Alteration Missense mutation
p.I491M (c.1473A>G)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Inhibition hsa04010
In Vitro Model LIM1215 cells Colon Homo sapiens (Human) CVCL_2574
HEK 293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Promega assay
Mechanism Description MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade.
References
Ref 1 MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutationsSci Transl Med. 2016 Feb 3;8(324):324ra14. doi: 10.1126/scitranslmed.aad5640.

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