cpi203 profile

CPI203: a BET protein bromodomain inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	71291068
CHEMBL ID	4303293
SCHEMBL ID	14756224
MeSH ID	M000607493

Synonym
S7304
HY-15846
cpi 203
cpi-203 ,
gtpl7513
cpi203
1446144-04-2
(s)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide
AKOS025142092
ten 010
(6s)-4-(4-chlorophenyl)-2,3,9-trimethyl-6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide
AC-35354
SCHEMBL14756224
J-690180
8-{(1s)-1-[8-(trifluoromethyl)-7-{[cis-4-(trifluoromethyl)cyclohexyl]oxy}-2-naphthyl]ethyl}-8-azabicyclo[3.2.1]octane-3-carboxylic a cid
EX-A456
2-[(9s)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetraazatricyclo[8.3.0.0(2),?]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide
AS-74912
cpi203, >=98% (hplc)
mfcd27997886
NCGC00356071-09
SW219296-1
cpi203 (cpi-203)
~{n}-(2-aminophenyl)-4-[2-[(9~{s})-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.0^{2,6}]trideca-2(6),4,7,10,12-pentaen-9-yl]ethanoylamino]benzamide
Q27076908
2-[(9s)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide
CCG-268648
P8T ,
CHEMBL4303293 ,
6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-2,3,9-trimethyl-, (6s)-
BP-25351
bdbm50527598
WHC14404

Excerpt	Reference	Relevance
"Upon CPI203 treatment, simultaneous downregulation of MYC and BFL-1 further overcomes resistance to ABT-199 both in vitro and in vivo, engaging synergistic caspase-mediated apoptosis in DHL cultures and tumor xenografts."	( The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma. Campo, E; Chamorro-Jorganes, A; Colomer, D; Dlouhy, I; Esteve-Arenys, A; Gonzalez, D; Lopez-Guillermo, A; Martinez, A; Pérez-Galán, P; Rodriguez, V; Roué, G; Rymkiewicz, G; Salaverria, I; Valero, JG, 2018)	1.22

Excerpt	Reference	Relevance
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."	( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein. Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)	0.51

Protein	Taxonomy	Measurement	Average (µ)	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
PPM1D protein	Homo sapiens (human)	Potency	1.1709	0.0052	9.4661	32.9993	AID1347411
cytochrome P450 family 3 subfamily A polypeptide 4	Homo sapiens (human)	Potency	21.3174	0.0123	7.9835	43.2770	AID1645841
Interferon beta	Homo sapiens (human)	Potency	1.1709	0.0033	9.1582	39.8107	AID1347411
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Bromodomain-containing protein 4	Homo sapiens (human)	IC50 (µMol)	0.0920	0.0004	0.4032	9.0500	AID1605852
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
regulation of transcription by RNA polymerase II	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of G2/M transition of mitotic cell cycle	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of transcription elongation by RNA polymerase II	Bromodomain-containing protein 4	Homo sapiens (human)
chromatin organization	Bromodomain-containing protein 4	Homo sapiens (human)
DNA damage response	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of transcription elongation by RNA polymerase II	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of canonical NF-kappaB signal transduction	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of DNA-templated transcription	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Bromodomain-containing protein 4	Homo sapiens (human)
regulation of inflammatory response	Bromodomain-containing protein 4	Homo sapiens (human)
positive regulation of T-helper 17 cell lineage commitment	Bromodomain-containing protein 4	Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell activation involved in immune response	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway	Interferon beta	Homo sapiens (human)
cell surface receptor signaling pathway via JAK-STAT	Interferon beta	Homo sapiens (human)
response to virus	Interferon beta	Homo sapiens (human)
positive regulation of autophagy	Interferon beta	Homo sapiens (human)
cytokine-mediated signaling pathway	Interferon beta	Homo sapiens (human)
natural killer cell activation	Interferon beta	Homo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT protein	Interferon beta	Homo sapiens (human)
cellular response to interferon-beta	Interferon beta	Homo sapiens (human)
B cell proliferation	Interferon beta	Homo sapiens (human)
negative regulation of viral genome replication	Interferon beta	Homo sapiens (human)
innate immune response	Interferon beta	Homo sapiens (human)
positive regulation of innate immune response	Interferon beta	Homo sapiens (human)
regulation of MHC class I biosynthetic process	Interferon beta	Homo sapiens (human)
negative regulation of T cell differentiation	Interferon beta	Homo sapiens (human)
positive regulation of transcription by RNA polymerase II	Interferon beta	Homo sapiens (human)
defense response to virus	Interferon beta	Homo sapiens (human)
type I interferon-mediated signaling pathway	Interferon beta	Homo sapiens (human)
neuron cellular homeostasis	Interferon beta	Homo sapiens (human)
cellular response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
cellular response to virus	Interferon beta	Homo sapiens (human)
negative regulation of Lewy body formation	Interferon beta	Homo sapiens (human)
negative regulation of T-helper 2 cell cytokine production	Interferon beta	Homo sapiens (human)
positive regulation of apoptotic signaling pathway	Interferon beta	Homo sapiens (human)
response to exogenous dsRNA	Interferon beta	Homo sapiens (human)
B cell differentiation	Interferon beta	Homo sapiens (human)
natural killer cell activation involved in immune response	Interferon beta	Homo sapiens (human)
adaptive immune response	Interferon beta	Homo sapiens (human)
T cell activation involved in immune response	Interferon beta	Homo sapiens (human)
humoral immune response	Interferon beta	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
transcription cis-regulatory region binding	Bromodomain-containing protein 4	Homo sapiens (human)
p53 binding	Bromodomain-containing protein 4	Homo sapiens (human)
chromatin binding	Bromodomain-containing protein 4	Homo sapiens (human)
transcription coregulator activity	Bromodomain-containing protein 4	Homo sapiens (human)
transcription coactivator activity	Bromodomain-containing protein 4	Homo sapiens (human)
protein binding	Bromodomain-containing protein 4	Homo sapiens (human)
RNA polymerase II CTD heptapeptide repeat kinase activity	Bromodomain-containing protein 4	Homo sapiens (human)
enzyme binding	Bromodomain-containing protein 4	Homo sapiens (human)
lysine-acetylated histone binding	Bromodomain-containing protein 4	Homo sapiens (human)
RNA polymerase II C-terminal domain binding	Bromodomain-containing protein 4	Homo sapiens (human)
P-TEFb complex binding	Bromodomain-containing protein 4	Homo sapiens (human)
histone reader activity	Bromodomain-containing protein 4	Homo sapiens (human)
cytokine activity	Interferon beta	Homo sapiens (human)
cytokine receptor binding	Interferon beta	Homo sapiens (human)
type I interferon receptor binding	Interferon beta	Homo sapiens (human)
protein binding	Interferon beta	Homo sapiens (human)
chloramphenicol O-acetyltransferase activity	Interferon beta	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
condensed nuclear chromosome	Bromodomain-containing protein 4	Homo sapiens (human)
nucleus	Bromodomain-containing protein 4	Homo sapiens (human)
nucleoplasm	Bromodomain-containing protein 4	Homo sapiens (human)
extracellular space	Interferon beta	Homo sapiens (human)
extracellular region	Interferon beta	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (11)

Assay ID	Title	Year	Journal	Article
AID1605852	Inhibition of BRD4 (unknown origin)	2020	Journal of medicinal chemistry, 04-23, Volume: 63, Issue:8	Discovery of 8-Methyl-pyrrolo[1,2-
AID1296008	Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening	2020	SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1	Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346987	P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346986	P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen	2019	Molecular pharmacology, 11, Volume: 96, Issue:5	A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347160	Primary screen NINDS Rhodamine qHTS for Zika virus inhibitors	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347159	Primary screen GU Rhodamine qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay	2020	Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49	Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347412	qHTS assay to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: Counter screen cell viability and HiBit confirmation	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347411	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347414	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: Secondary screen by immunofluorescence	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347415	qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: tertiary screen by RT-qPCR	2020	ACS chemical biology, 07-17, Volume: 15, Issue:7	High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1345665	Human bromodomain containing 4 (Bromodomain kinase (BRDK) family)	2012	Proceedings of the National Academy of Sciences of the United States of America, May-01, Volume: 109, Issue:18	BRD4 is an atypical kinase that phosphorylates serine2 of the RNA polymerase II carboxy-terminal domain.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	12 (57.14)	24.3611
2020's	9 (42.86)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	21 (100.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
thalidomide Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.	2.15	1	phthalimides; piperidones
triazoles Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.	2.17	1	1,2,3-triazole
imatinib mesylate imatinib methanesulfonate : A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.	2.13	1	methanesulfonate salt	anticoronaviral agent; antineoplastic agent; apoptosis inducer; tyrosine kinase inhibitor
lenalidomide [no description available]	7.15	1	aromatic amine; dicarboximide; isoindoles; piperidones	angiogenesis inhibitor; antineoplastic agent; immunomodulator
bortezomib [no description available]	7.11	1	amino acid amide; L-phenylalanine derivative; pyrazines	antineoplastic agent; antiprotozoal drug; protease inhibitor; proteasome inhibitor
sirolimus Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.	2.1	1	antibiotic antifungal drug; cyclic acetal; cyclic ketone; ether; macrolide lactam; organic heterotricyclic compound; secondary alcohol	antibacterial drug; anticoronaviral agent; antineoplastic agent; bacterial metabolite; geroprotector; immunosuppressive agent; mTOR inhibitor
6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6s)- [no description available]	2.25	1	organonitrogen heterocyclic compound; organosulfur heterocyclic compound
jq1 compound [no description available]	2.25	1	carboxylic ester; organochlorine compound; tert-butyl ester; thienotriazolodiazepine	angiogenesis inhibitor; anti-inflammatory agent; antineoplastic agent; apoptosis inducer; bromodomain-containing protein 4 inhibitor; cardioprotective agent; ferroptosis inducer
abt-199 venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.. venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.	7.17	1	aromatic ether; C-nitro compound; monochlorobenzenes; N-alkylpiperazine; N-arylpiperazine; N-sulfonylcarboxamide; oxanes; pyrrolopyridine	antineoplastic agent; apoptosis inducer; B-cell lymphoma 2 inhibitor
rg7112 [no description available]	2.13	1
cyclin d1 Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.	2.17	1

Condition	Relationship Strength	Studies
Congenital Zika Syndrome [description not available]	2.25	1
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	2.59	2
Zika Virus Infection A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.	2.25	1
Cancer of Lung [description not available]	2.41	1
Lung Neoplasms Tumors or cancer of the LUNG.	2.41	1
Acute Myelogenous Leukemia [description not available]	2.31	1
Leukemia, Myeloid, Acute Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.	2.31	1
Cancer of Pancreas [description not available]	2.25	1
Carcinoma, Ductal, Pancreatic [description not available]	2.25	1
Pancreatic Neoplasms Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	2.25	1
Carcinoma, Pancreatic Ductal Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.	2.25	1
Gambling, Pathologic [description not available]	2.25	1
Gambling An activity distinguished primarily by an element of risk in trying to obtain a desired goal, e.g., playing a game of chance for money.	2.25	1
Kahler Disease [description not available]	2.53	2
Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.	2.53	2
Carcinoma, Epidermoid [description not available]	2.17	1
Cancer of Skin [description not available]	2.17	1
Carcinoma, Squamous Cell A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)	2.17	1
Skin Neoplasms Tumors or cancer of the SKIN.	2.17	1
Germinoblastoma [description not available]	2.17	1
Lymphoma A general term for various neoplastic diseases of the lymphoid tissue.	7.17	1
Diffuse Large B-Cell Lymphoma [description not available]	2.21	1
Lymphoma, Large B-Cell, Diffuse Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.	2.21	1
Cancer of Ovary [description not available]	2.21	1
Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.	2.21	1
Neuroendocrine Tumors Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.	7.1	1
Granulocytic Leukemia, Chronic [description not available]	2.13	1
Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.	2.13	1

cpi203

Description

Cross-References

Synonyms (33)

Research Excerpts

Treatment

Bioavailability

Protein Targets (4)

Potency Measurements

Inhibition Measurements

Biological Processes (39)

Molecular Functions (16)

Ceullar Components (5)

Bioassays (11)

Research

Studies (21)

Market Indicators

Research Demand Index: 25.00

Study Types

cpi203

Description

Cross-References

Synonyms (33)

Research Excerpts

Treatment

Bioavailability

Protein Targets (4)

Potency Measurements

Inhibition Measurements

Biological Processes (39)

Molecular Functions (16)

Ceullar Components (5)

Bioassays (11)

Research

Studies (21)

Market Indicators

Research Demand Index: 25.00

Study Types

Related Drugs (11)

Related Conditions (28)