Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT7GN3U)

• DTT Name: Apolipoprotein A-I (APOA1)
• Synonyms: Truncated apolipoprotein AI; Apolipoprotein A1; ApoAI; ApoA-I; Apo-AI
• Gene Name: APOA1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Apolipoprotein
• UniProt ID: APOA1_HUMAN
• TTD ID: T56545
• Sequence:
  MKAAVLTLAVLFLTGSQARHFWQQDEPPQSPWDRVKDLATVYVDVLKDSGRDYVSQFEGS
  ALGKQLNLKLLDNWDSVTSTFSKLREQLGPVTQEFWDNLEKETEGLRQEMSKDLEEVKAK
  VQPYLDDFQKKWQEEMELYRQKVEPLRAELQEGARQKLHELQEKLSPLGEEMRDRARAHV
  DALRTHLAPYSDELRQRLAARLEALKENGGARLAEYHAKATEHLSTLSEKAKPALEDLRQ
  GLLPVLESFKVSFLSALEEYTKKLNTQ
• Function: As part of the SPAP complex, activates spermatozoa motility. Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT).
• KEGG Pathway:
  PPAR signaling pathway (hsa03320)
  Fat digestion and absorption (hsa04975)
  Vitamin digestion and absorption (hsa04977)
  African trypanosomiasis (hsa05143)
• Reactome Pathway:
  ABC transporters in lipid homeostasis (R-HSA-1369062)
  Chylomicron-mediated lipid transport (R-HSA-174800)
  HDL-mediated lipid transport (R-HSA-194223)
  PPARA activates gene expression (R-HSA-1989781)
  Scavenging of heme from plasma (R-HSA-2168880)
  Scavenging by Class B Receptors (R-HSA-3000471)
  Scavenging by Class A Receptors (R-HSA-3000480)
  Retinoid metabolism and transport (R-HSA-975634)
  Amyloid formation (R-HSA-977225)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DTT

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CER-001	DMWUQI9	Acute coronary syndrome	BA41	Phase 2	[2]
CSL-112	DMZCG91	Arteriosclerosis	BD40	Phase 2	[1]
CER-522	DMGAW0H	Aortic valve stenosis	BB70	Phase 1	[3]
MDCO-216	DMAQ24G	Arteriosclerosis	BD40	Phase 1	[4]

4 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CRD-5	DMVU4A5	Hyperlipidaemia	5C80	Discontinued in Phase 2	[5]
APP-018	DM5L9I2	Arteriosclerosis	BD40	Discontinued in Phase 1	[6]
AMT-050	DMMKOCL	Cholesterol metabolism disorder	5C8Z	Terminated	[7]
LSI-518P	DMFJPYV	Cardiovascular disease	BA00-BE2Z	Terminated	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	8.72E-01	-0.03	-0.45
Coronary artery disease	BA80-BA8Z	Peripheral blood	1.44E-01	0.17	1.01
Aortic stenosis	BA80-BA8Z	Calcified aortic valve	2.95E-01	-0.25	-0.24

References

• [1] CER-001, a HDL-mimetic, stimulates the reverse lipid transport and atherosclerosis regression in high cholesterol diet-fed LDL-receptor deficient mice. Atherosclerosis. 2014 Jan;232(1):110-8.
• [2] Clinical pipeline report, company report or official report of Cerenis.
• [3] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033541)
• [4] MDCO-216 (Apo A-I Milano/POPC Complex) Administered to Cynomolgus Monkeys Induces Pronounced Changes in Plasma Lipids and Apolipoproteins. Circulation. 2011; 124: A10978.
• [5] Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 2008 Jun;13(2):363-81.
• [6] Apolipoprotein A-I and its mimetics for the treatment of atherosclerosis. Curr Opin Investig Drugs. 2010 September; 11(9): 989-996.
• [7] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026835)
• [8] Clinical review: The evolving role of HDL in the treatment of high-risk patients with cardiovascular disease. J Clin Endocrinol Metab. 2011 May;96(5):1246-57.