Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUS1RD)

• DTT Name: Microsomal triglyceride transfer protein (MTTP)
• Synonyms: Microsomal triglyceride transfer protein large subunit; MTP
• Gene Name: MTTP
• DTT Type: Successful target; [1]
• UniProt ID: MTP_HUMAN
• TTD ID: T46628
• Sequence:
  MILLAVLFLCFISSYSASVKGHTTGLSLNNDRLYKLTYSTEVLLDRGKGKLQDSVGYRIS
  SNVDVALLWRNPDGDDDQLIQITMKDVNVENVNQQRGEKSIFKGKSPSKIMGKENLEALQ
  RPTLLHLIHGKVKEFYSYQNEAVAIENIKRGLASLFQTQLSSGTTNEVDISGNCKVTYQA
  HQDKVIKIKALDSCKIARSGFTTPNQVLGVSSKATSVTTYKIEDSFVIAVLAEETHNFGL
  NFLQTIKGKIVSKQKLELKTTEAGPRLMSGKQAAAIIKAVDSKYTAIPIVGQVFQSHCKG
  CPSLSELWRSTRKYLQPDNLSKAEAVRNFLAFIQHLRTAKKEEILQILKMENKEVLPQLV
  DAVTSAQTSDSLEAILDFLDFKSDSSIILQERFLYACGFASHPNEELLRALISKFKGSIG
  SSDIRETVMIITGTLVRKLCQNEGCKLKAVVEAKKLILGGLEKAEKKEDTRMYLLALKNA
  LLPEGIPSLLKYAEAGEGPISHLATTALQRYDLPFITDEVKKTLNRIYHQNRKVHEKTVR
  TAAAAIILNNNPSYMDVKNILLSIGELPQEMNKYMLAIVQDILRFEMPASKIVRRVLKEM
  VAHNYDRFSRSGSSSAYTGYIERSPRSASTYSLDILYSGSGILRRSNLNIFQYIGKAGLH
  GSQVVIEAQGLEALIAATPDEGEENLDSYAGMSAILFDVQLRPVTFFNGYSDLMSKMLSA
  SGDPISVVKGLILLIDHSQELQLQSGLKANIEVQGGLAIDISGAMEFSLWYRESKTRVKN
  RVTVVITTDITVDSSFVKAGLETSTETEAGLEFISTVQFSQYPFLVCMQMDKDEAPFRQF
  EKKYERLSTGRGYVSQKRKESVLAGCEFPLHQENSEMCKVVFAPQPDSTSSGWF
• Function: Required for the secretion of plasma lipoproteins that contain apolipoprotein B. Catalyzes the transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces.
• KEGG Pathway: Fat digestion and absorption (hsa04975)
• Reactome Pathway: Chylomicron-mediated lipid transport (R-HSA-174800)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-201038	DMQTAGO	Familial hypercholesterolemia	5C80.00	Approved	[1]

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Granotapide	DMMZQ7V	Hyperlipidaemia	5C80	Phase 2	[2]
Implitapide	DMTN16K	Hyperlipidaemia	5C80	Phase 2	[3]
JNJ-16269110	DMPFG7H	Type-2 diabetes	5A11	Phase 2	[4]
SLx-4090	DMM3AI8	Diabetic complication	5A2Y	Phase 2	[5]
KD020	DMZ416B	Kidney disease	GC2Z	Phase 1/2	[6]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GR-328713	DMUANK9	Arteriosclerosis	BD40	Discontinued in Phase 1	[7]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DIRLOTAPIDE	DM2MV9O	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	9.76E-02	0.13	0.68
Familial hypercholesterolemia	5A11	Whole blood	2.59E-02	-0.15	-0.71
Coronary artery disease	BA80-BA8Z	Peripheral blood	2.25E-01	0.07	1.33

References

• [1] Dyslipidemia and cardiovascular diseases. Curr Opin Lipidol. 2009 Apr;20(2):157-8.
• [2] JTT-130, a novel intestine-specific inhibitor of microsomal triglyceride transfer protein, suppresses food intake and gastric emptying with the elevation of plasma peptide YY and glucagon-like peptide-1 in a dietary fat-dependent manner. J Pharmacol Exp Ther. 2011 Mar;336(3):850-6.
• [3] Novel nonstatin strategies to lower low-density lipoprotein cholesterol. Curr Atheroscler Rep. 2009 Jan;11(1):67-70.
• [4] ClinicalTrials.gov (NCT00672386) A Study of the Safety and Effectiveness of a R256918 in Patients With Type 2 Diabetes. U.S. National Institutes of Health.
• [5] A small-molecule inhibitor of enterocytic microsomal triglyceride transfer protein, SLx-4090: biochemical, pharmacodynamic, pharmacokinetic, and safety profile. J Pharmacol Exp Ther. 2011 Jun;337(3):775-85.
• [6] Clinical pipeline report, company report or official report of Kadmon Pharmaceuticals.
• [7] Patent CN101237870 B.
• [8] In vitro and in vivo profile of 5-[(4'-trifluoromethyl-biphenyl-2-carbonyl)-amino]-1H-indole-2-carboxylic acid benzylmethyl carbamoylamide (dirlota... Bioorg Med Chem Lett. 2007 Apr 1;17(7):1996-9.