Compound Detail
CHEMBL4213970
MK-8353 Phase I
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Phase I
CS[C@@]1(C(=O)Nc2ccc3[nH]nc(-c4ccc(OC(C)C)nc4)c3c2)CCN(CC(=O)N2CC=C(c3ccc(-c4ncn(C)n4)cc3)CC2)C1
Basic Information
| ChEMBL ID | CHEMBL4213970 |
| Name | MK-8353 |
| Phase | Phase I |
| Structure Type | MOL |
| InChI Key | KPQQGHGDBBJGFA-QNGWXLTQSA-N |
7
Targets
7
Activities
1
Assay Types
30
PK Parameters
20
Publications
2
Known Names
2
Indications
2
Mechanisms
Molecular Properties
691.9
MW (Da)
5.27
ALogP
10
HBA
2
HBD
134.2
PSA (Ų)
0.20
QED
2
Ro5 Violations
10
Rot. Bonds
Drug Information
| Molecule Type | Small molecule |
| Chirality | Single Enantiomer |
Mechanism of Action
| Mechanism | Action Type | Target | Direct | Efficacy |
|---|---|---|---|---|
| MAP kinase ERK1 inhibitor | INHIBITOR | Mitogen-activated protein kinase 3 | ✓ | ✓ |
| MAP kinase ERK2 inhibitor | INHIBITOR | Mitogen-activated protein kinase 1 | ✓ | ✓ |
Indications
Colorectal Neoplasms Neoplasms
Activity Summary
IC50 7 meas. best 8.15
Target Activity Profile
| Target | Type | Best pChEMBL | Mean pChEMBL | Best (nM) | # Data |
|---|---|---|---|---|---|
| Mitogen-activated protein kinase 1 CHEMBL4040 | IC50 | 8.15 | 8.15 | 7.0 | 1 |
| Mitogen-activated protein kinase 3 CHEMBL3385 | IC50 | 7.7 | 7.7 | 20.0 | 1 |
| COLO 205 CHEMBL614561 | IC50 | 7.64 | 7.64 | 23.0 | 1 |
| HT-29 CHEMBL384 | IC50 | 7.29 | 7.29 | 51.0 | 1 |
| A2058 CHEMBL613503 | IC50 | 6.43 | 6.43 | 371.0 | 1 |
| Cytochrome P450 3A4 CHEMBL340 | IC50 | 5.77 | 5.77 | 1700.0 | 1 |
| Cytochrome P450 2C8 CHEMBL3721 | IC50 | 5.46 | 5.46 | 3500.0 | 1 |
Pharmacokinetic Data
| Parameter | Value | Units | Species |
|---|---|---|---|
| AUC | 23869.17 | ng.hr.mL-1 | Rattus norvegicus |
| AUC | 13422.08 | ng.hr.mL-1 | Mus musculus |
| AUC | 58808.1 | ng.hr.mL-1 | Rattus norvegicus |
| AUC | 13837.2 | ng.hr.mL-1 | Canis lupus familiaris |
| AUC | 899.42 | ng.hr.mL-1 | Macaca mulatta |
| AUC | 10585.46 | ng.hr.mL-1 | Mus musculus |
| AUC | 98935.98 | ng.hr.mL-1 | Rattus norvegicus |
| AUC | 31133.7 | ng.hr.mL-1 | Canis lupus familiaris |
| AUC | 138.37 | ng.hr.mL-1 | Macaca mulatta |
| CL | 38.0 | mL.min-1.kg-1 | Mus musculus |
| CL | 1.0 | mL.min-1.kg-1 | Rattus norvegicus |
| CL | 3.9 | mL.min-1.kg-1 | Canis lupus familiaris |
| CL | 17.9 | mL.min-1.kg-1 | Macaca mulatta |
| Cmax | 4600.0 | nM | Mus musculus |
| Cmax | 24000.0 | nM | Rattus norvegicus |
| Cmax | 6500.0 | nM | Canis lupus familiaris |
| Cmax | 60.0 | nM | Macaca mulatta |
| F | 80.0 | % | Mus musculus |
| F | 50.0 | % | Rattus norvegicus |
| F | 23.0 | % | Canis lupus familiaris |
| F | 2.0 | % | Macaca mulatta |
| MRT | 1.5 | hr | Mus musculus |
| MRT | 2.3 | hr | Rattus norvegicus |
| MRT | 4.0 | hr | Canis lupus familiaris |
| MRT | 1.9 | hr | Macaca mulatta |
| T1/2 | 1.8 | hr | Mus musculus |
| T1/2 | 1.6 | hr | Rattus norvegicus |
| T1/2 | 2.8 | hr | Canis lupus familiaris |
| T1/2 | 1.3 | hr | Macaca mulatta |
| Tmax | 1.0 | hr | Mus musculus |
Activity Data Samples
Top measurements by pChEMBL value
| Target | Type | Rel. | Value | Units | pChEMBL | Assay | PubMed |
|---|---|---|---|---|---|---|---|
| Mitogen-activated protein kinase 1 | IC50 | = | 7.0 | nM | 8.15 | Inhibition of ERK2 (unknown origin) using peptide substrate measured after 45 mi... | 30034615 |
| Mitogen-activated protein kinase 3 | IC50 | = | 20.0 | nM | 7.7 | Inhibition of ERK1 (unknown origin) using peptide substrate measured after 45 mi... | 30034615 |
| COLO 205 | IC50 | = | 23.0 | nM | 7.64 | Antiproliferative activity against human COLO205 cells harboring BRAF V600E/D mu... | 30034615 |
| HT-29 | IC50 | = | 51.0 | nM | 7.29 | Antiproliferative activity against human HT-29 cells harboring BRAF V600E/D muta... | 30034615 |
| A2058 | IC50 | = | 371.0 | nM | 6.43 | Antiproliferative activity against human A2058 cells harboring BRAF V600E/D muta... | 30034615 |
| Cytochrome P450 3A4 | IC50 | = | 1700.0 | nM | 5.77 | Inhibition of CYP3A4 (unknown origin) preincubated followed by substrate additio... | 30034615 |
| Cytochrome P450 2C8 | IC50 | = | 3500.0 | nM | 5.46 | Inhibition of CYP2C8 (unknown origin) preincubated followed by substrate additio... | 30034615 |
Literature References
Data from ChEMBL 36 via Core Engine