This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Ulixertinib
Accession Number
DB13930
Type
Small Molecule
Groups
Investigational
Description

Ulixertinib is a a novel, reversible, ATP-competitive ERK1/2 inhibitor with high potency and ERK1/2 selectivity [1]. It is currently in clinical trials for the treatment of a wide range of tumors.

Structure
Thumb
Synonyms
Not Available
External IDs
BVD-523 / BVD-ERK
Product Ingredients
IngredientUNIICASInChI Key
Ulixertinib hydrochloride3K792HRQ8B1956366-10-1DKGYQCPFBWFTHM-FSRHSHDFSA-N
Categories
Not Available
UNII
16ZDH50O1U
CAS number
869886-67-9
Weight
Average: 433.33
Monoisotopic: 432.1119814
Chemical Formula
C21H22Cl2N4O2
InChI Key
KSERXGMCDHOLSS-LJQANCHMSA-N
InChI
InChI=1S/C21H22Cl2N4O2/c1-12(2)26-20-8-16(17(23)10-25-20)14-7-18(24-9-14)21(29)27-19(11-28)13-4-3-5-15(22)6-13/h3-10,12,19,24,28H,11H2,1-2H3,(H,25,26)(H,27,29)/t19-/m1/s1
IUPAC Name
4-{5-chloro-2-[(propan-2-yl)amino]pyridin-4-yl}-N-[(1S)-1-(3-chlorophenyl)-2-hydroxyethyl]-1H-pyrrole-2-carboxamide
SMILES
[H]N([C@H](CO)C1=CC(Cl)=CC=C1)C(=O)C1=CC(=CN1[H])C1=CC(=NC=C1Cl)N([H])C(C)C

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UMitogen-activated protein kinase 3
inhibitor
Human
UMitogen-activated protein kinase 1
inhibitor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ: Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. [PubMed:28939558]
External Links
ChemSpider
9893722
ChEMBL
CHEMBL3590106
HET
EVK
PDB Entries
6gdq

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherHealthy Volunteers1
1RecruitingTreatmentCancer of Pancreas / Cancer of the Pancreas / Malignant Neoplasm of Pancreas1
1RecruitingTreatmentMalignant Neoplasm of Pancreas / Tumors, Solid1
1, 2CompletedTreatmentAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
1, 2CompletedTreatmentAdvanced Solid Tumors1
2RecruitingScreeningAdvanced Malignant Solid Neoplasm / Ann Arbor Stage III Childhood Non-Hodgkin Lymphoma / Ann Arbor Stage IV Childhood Non-Hodgkin Lymphoma / Childhood Langerhans Cell Histiocytosis / Histiocytic Sarcoma (HS) / Juvenile Xanthogranuloma / Langerhans Cell Histiocytosis (LCH) / Malignant Gliomas / Malignant Lymphomas / Recurrent Central Nervous System Neoplasm / Recurrent Childhood Ependymoma / Recurrent Childhood Malignant Germ Cell Tumor / Recurrent Childhood Medulloblastoma / Recurrent Childhood Non-Hodgkin Lymphoma / Recurrent Childhood Rhabdomyosarcoma / Recurrent Childhood Soft Tissue Sarcoma / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Solid Neoplasm / Recurrent Neuroblastoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Rhabdoid Tumor / Refractory Central Nervous System Neoplasm / Refractory Childhood Malignant Germ Cell Tumor / Refractory Ewing Sarcoma / Refractory Glioma / Refractory Hepatoblastoma / Refractory Langerhans cell histiocytosis / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Rhabdoid Tumors / Stage III Childhood Non-Hodgkin Lymphoma / Stage III Osteosarcoma / Stage III Osteosarcoma AJCC v7 / Stage III Soft Tissue Sarcoma / Stage III Soft Tissue Sarcoma AJCC v7 / Stage IV Childhood Non-Hodgkin Lymphoma / Stage IV Osteosarcoma / Stage IV Osteosarcoma AJCC v7 / Stage IV Soft Tissue Sarcoma / Stage IV Soft Tissue Sarcoma AJCC v7 / Stage IVA Osteosarcoma / Stage IVA Osteosarcoma AJCC v7 / Stage IVB Osteosarcoma / Stage IVB Osteosarcoma AJCC v7 / Wilms' tumor1
2RecruitingTreatmentAdvanced Malignant Solid Neoplasm / ARAF Gene Mutation / BRAF Gene Mutation / GNA11 Gene Mutation / GNAQ Gene Mutation / HRAS Gene Mutation / KRAS Gene Mutation / MAP2K1 Gene Mutation / MAPK1 Gene Mutation / NF1 Gene Mutation / NRAS Gene Mutation / Recurrent Ependymal Tumor / Recurrent Ewing Sarcoma / Recurrent Gliomas / Recurrent Hepatoblastoma / Recurrent Histiocytic and Dendritic Cell Neoplasm / Recurrent Langerhans Cell Histiocytosis / Recurrent Malignant Central Nervous System Neoplasm / Recurrent Malignant Germ Cell Tumor / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Rhabdoid Tumor / Recurrent Rhabdomyosarcoma / Recurrent Soft Tissue Sarcoma / Refractory Ependymoma / Refractory Ewing Sarcoma / Refractory Glioma / Refractory Hepatoblastoma / Refractory Histiocytic and Dendritic Cell Neoplasm / Refractory Langerhans cell histiocytosis / Refractory Malignant Central Nervous System Neoplasm / Refractory Malignant Germ Cell Tumor / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Refractory Soft Tissue Sarcoma / Wilms' tumor1
2RecruitingTreatmentUveal Melanoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00447 mg/mLALOGPS
logP4.09ALOGPS
logP3.62ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)12.78ChemAxon
pKa (Strongest Basic)4.65ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area90.04 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity117.51 m3·mol-1ChemAxon
Polarizability44.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
High potency and ERK1/2 selectivity
General Function
Phosphatase binding
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK3
Uniprot ID
P27361
Uniprot Name
Mitogen-activated protein kinase 3
Molecular Weight
43135.16 Da
References
  1. Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ: Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. [PubMed:28939558]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
High potency and ERK1/2 selectivity
General Function
Rna polymerase ii carboxy-terminal domain kinase activity
Specific Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK ca...
Gene Name
MAPK1
Uniprot ID
P28482
Uniprot Name
Mitogen-activated protein kinase 1
Molecular Weight
41389.265 Da
References
  1. Germann UA, Furey BF, Markland W, Hoover RR, Aronov AM, Roix JJ, Hale M, Boucher DM, Sorrell DA, Martinez-Botella G, Fitzgibbon M, Shapiro P, Wick MJ, Samadani R, Meshaw K, Groover A, DeCrescenzo G, Namchuk M, Emery CM, Saha S, Welsch DJ: Targeting the MAPK Signaling Pathway in Cancer: Promising Preclinical Activity with the Novel Selective ERK1/2 Inhibitor BVD-523 (Ulixertinib). Mol Cancer Ther. 2017 Nov;16(11):2351-2363. doi: 10.1158/1535-7163.MCT-17-0456. Epub 2017 Sep 22. [PubMed:28939558]

Drug created on December 18, 2017 09:38 / Updated on November 02, 2018 09:13