Target Information

Target General Information

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Target ID

T47387 (Former ID: TTDI02260)

Target Name

BCL-2 messenger RNA (BCL2 mRNA)

Synonyms

Bcl-2 (mRNA); Apoptosis regulator Bcl-2 (mRNA)

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Gene Name

BCL2

Target Type

Clinical trial target

[1]

Disease

[+] 4 Target-related Diseases

Diffuse large B-cell lymphoma [ICD-11: 2A81]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Leukaemia [ICD-11: 2A60-2B33]

Malignant haematopoietic neoplasm [ICD-11: 2B33]

Function

Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release. Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells.

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BioChemical Class

mRNA target

UniProt ID

BCL2_HUMAN

Sequence

MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPA
ASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLH
LTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEY
LNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK

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Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

PNT-2258

Drug Info

Phase 2

Solid tumour/cancer

[2]

Beclanorsen

Drug Info

Phase 1/2

leukaemia

[3]

BP1002

Drug Info

Phase 1

Haematopoietic/lymphoid cancer

[4]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

BP1002

Drug Info

[6]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 20 KEGG Pathways	+
1	NF-kappa B signaling pathway
2	HIF-1 signaling pathway
3	Sphingolipid signaling pathway
4	Protein processing in endoplasmic reticulum
5	PI3K-Akt signaling pathway
6	Apoptosis
7	Adrenergic signaling in cardiomyocytes
8	Focal adhesion
9	Neurotrophin signaling pathway
10	Cholinergic synapse
11	Amyotrophic lateral sclerosis (ALS)
12	Toxoplasmosis
13	Tuberculosis
14	Hepatitis B
15	Epstein-Barr virus infection
16	Pathways in cancer
17	MicroRNAs in cancer
18	Colorectal cancer
19	Prostate cancer
20	Small cell lung cancer
NetPath Pathway	[+] 7 NetPath Pathways	+
1	IL5 Signaling Pathway
2	TCR Signaling Pathway
3	IL2 Signaling Pathway
4	IL3 Signaling Pathway
5	Leptin Signaling Pathway
6	RANKL Signaling Pathway
7	TSLP Signaling Pathway
Panther Pathway	[+] 3 Panther Pathways	+
1	Apoptosis signaling pathway
2	Oxidative stress response
3	CCKR signaling map ST
PID Pathway	[+] 14 PID Pathways	+
1	Role of Calcineurin-dependent NFAT signaling in lymphocytes
2	IL2-mediated signaling events
3	IL2 signaling events mediated by PI3K
4	Ceramide signaling pathway
5	Direct p53 effectors
6	RXR and RAR heterodimerization with other nuclear receptor
7	ATF-2 transcription factor network
8	C-MYB transcription factor network
9	HIV-1 Nef: Negative effector of Fas and TNF-alpha
10	Caspase Cascade in Apoptosis
11	Signaling events mediated by Stem cell factor receptor (c-Kit)
12	EPO signaling pathway
13	IL2 signaling events mediated by STAT5
14	Validated targets of C-MYC transcriptional repression
Reactome	[+] 3 Reactome Pathways	+
1	Activation of BAD and translocation to mitochondria
2	BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members
3	The NLRP1 inflammasome
WikiPathways	[+] 24 WikiPathways	+
1	DNA Damage Response (only ATM dependent)
2	Senescence and Autophagy in Cancer
3	IL-2 Signaling Pathway
4	FAS pathway and Stress induction of HSP regulation
5	Kit receptor signaling pathway
6	IL-3 Signaling Pathway
7	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
8	Apoptosis
9	Nanoparticle triggered autophagic cell death
10	Amyotrophic lateral sclerosis (ALS)
11	Integrated Pancreatic Cancer Pathway
12	Corticotropin-releasing hormone
13	Interleukin-11 Signaling Pathway
14	Prostate Cancer
15	miR-targeted genes in muscle cell - TarBase
16	miR-targeted genes in lymphocytes - TarBase
17	miR-targeted genes in leukocytes - TarBase
18	Integrated Breast Cancer Pathway
19	Integrated Cancer pathway
20	Intrinsic Pathway for Apoptosis
21	Apoptosis Modulation and Signaling
22	TP53 Network
23	Influenza A virus infection
24	IL-5 Signaling Pathway

References

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REF 1

Clinical pipeline report, company report or official report of ProNAi.

REF 2

ClinicalTrials.gov (NCT01733238) Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT00285103) SPC2996 in Chronic Lymphocytic Leukaemia. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT04072458) A Clinical Trial of BP1002 in Patients With Advanced Lymphoid Malignancies. U.S. National Institutes of Health.

REF 5

Combination of novel imidazopyridazine mps-1 kinase inhibitors and bcl-2 family protein inhibitors. ACS Med Chem Lett. 2014 Jul 30;6(1):7-8.

REF 6

Clinical pipeline report, company report or official report of Bio-Path Holdings.

REF 7

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2844).

REF 8

Design and development of antisense drugs. Expert Opin. Drug Discov. 2008 3(10):1189-1207.

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