Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJGY7A)

• DTT Name: Complement C3 (CO3)
• Synonyms: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1; C3
• Gene Name: C3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Complement system
• UniProt ID: CO3_HUMAN
• TTD ID: T26851
• Sequence:
  MGPTSGPSLLLLLLTHLPLALGSPMYSIITPNILRLESEETMVLEAHDAQGDVPVTVTVH
  DFPGKKLVLSSEKTVLTPATNHMGNVTFTIPANREFKSEKGRNKFVTVQATFGTQVVEKV
  VLVSLQSGYLFIQTDKTIYTPGSTVLYRIFTVNHKLLPVGRTVMVNIENPEGIPVKQDSL
  SSQNQLGVLPLSWDIPELVNMGQWKIRAYYENSPQQVFSTEFEVKEYVLPSFEVIVEPTE
  KFYYIYNEKGLEVTITARFLYGKKVEGTAFVIFGIQDGEQRISLPESLKRIPIEDGSGEV
  VLSRKVLLDGVQNPRAEDLVGKSLYVSATVILHSGSDMVQAERSGIPIVTSPYQIHFTKT
  PKYFKPGMPFDLMVFVTNPDGSPAYRVPVAVQGEDTVQSLTQGDGVAKLSINTHPSQKPL
  SITVRTKKQELSEAEQATRTMQALPYSTVGNSNNYLHLSVLRTELRPGETLNVNFLLRMD
  RAHEAKIRYYTYLIMNKGRLLKAGRQVREPGQDLVVLPLSITTDFIPSFRLVAYYTLIGA
  SGQREVVADSVWVDVKDSCVGSLVVKSGQSEDRQPVPGQQMTLKIEGDHGARVVLVAVDK
  GVFVLNKKNKLTQSKIWDVVEKADIGCTPGSGKDYAGVFSDAGLTFTSSSGQQTAQRAEL
  QCPQPAARRRRSVQLTEKRMDKVGKYPKELRKCCEDGMRENPMRFSCQRRTRFISLGEAC
  KKVFLDCCNYITELRRQHARASHLGLARSNLDEDIIAEENIVSRSEFPESWLWNVEDLKE
  PPKNGISTKLMNIFLKDSITTWEILAVSMSDKKGICVADPFEVTVMQDFFIDLRLPYSVV
  RNEQVEIRAVLYNYRQNQELKVRVELLHNPAFCSLATTKRRHQQTVTIPPKSSLSVPYVI
  VPLKTGLQEVEVKAAVYHHFISDGVRKSLKVVPEGIRMNKTVAVRTLDPERLGREGVQKE
  DIPPADLSDQVPDTESETRILLQGTPVAQMTEDAVDAERLKHLIVTPSGCGEQNMIGMTP
  TVIAVHYLDETEQWEKFGLEKRQGALELIKKGYTQQLAFRQPSSAFAAFVKRAPSTWLTA
  YVVKVFSLAVNLIAIDSQVLCGAVKWLILEKQKPDGVFQEDAPVIHQEMIGGLRNNNEKD
  MALTAFVLISLQEAKDICEEQVNSLPGSITKAGDFLEANYMNLQRSYTVAIAGYALAQMG
  RLKGPLLNKFLTTAKDKNRWEDPGKQLYNVEATSYALLALLQLKDFDFVPPVVRWLNEQR
  YYGGGYGSTQATFMVFQALAQYQKDAPDHQELNLDVSLQLPSRSSKITHRIHWESASLLR
  SEETKENEGFTVTAEGKGQGTLSVVTMYHAKAKDQLTCNKFDLKVTIKPAPETEKRPQDA
  KNTMILEICTRYRGDQDATMSILDISMMTGFAPDTDDLKQLANGVDRYISKYELDKAFSD
  RNTLIIYLDKVSHSEDDCLAFKVHQYFNVELIQPGAVKVYAYYNLEESCTRFYHPEKEDG
  KLNKLCRDELCRCAEENCFIQKSDDKVTLEERLDKACEPGVDYVYKTRLVKVQLSNDFDE
  YIMAIEQTIKSGSDEVQVGQQRTFISPIKCREALKLEEKKHYLMWGLSSDFWGEKPNLSY
  IIGKDTWVEHWPEEDECQDEENQKQCQDLGAFTESMVVFGCPN
• Function: Acylation stimulating protein: adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).
• KEGG Pathway:
  Phagosome (hsa04145)
  Complement and coagulation cascades (hsa04610)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Staphylococcus aureus infection (hsa05150)
  Tuberculosis (hsa05152)
  Herpes simplex infection (hsa05168)
  Viral carcinogenesis (hsa05203)
  Systemic lupus erythematosus (hsa05322)
• Reactome Pathway:
  Activation of C3 and C5 (R-HSA-174577)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)
  Peptide ligand-binding receptors (R-HSA-375276)
  G alpha (i) signalling events (R-HSA-418594)
  Regulation of Complement cascade (R-HSA-977606)
  Alternative complement activation (R-HSA-173736)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pegcetacoplan	DM4HQ52	Paroxysmal nocturnal haemoglobinuria	3A21.0	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Imprime PGG	DMIUA3M	Non-hodgkin lymphoma	2B33.5	Phase 2/3	[2]
AMY-101	DMS0GA6	Gingivitis	DA0B	Phase 2	[3]
NGM621	DM84DP5	Geographic atrophy	9B75	Phase 2	[4]
POT-4	DMH0LM2	Macular degeneration	9B78.3	Phase 2	[5]

28 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ac-ICV(1MeW)QDWGAHRCT-NH2	DM351NL	Discovery agent	N.A.	Investigative	[6]
Ac-ICV(5fW)QDWGAHRCT-NH2	DMQLPGA	Discovery agent	N.A.	Investigative	[6]
Ac-ICV(5MeW)QDWGAHRCT-NH2	DM52T90	Discovery agent	N.A.	Investigative	[6]
Ac-ICVWQD(5fW)GAHRCT-NH2	DMPK9LG	Discovery agent	N.A.	Investigative	[6]
Ac-ICVWQDWGAHRCT-NH2	DMPSI26	Discovery agent	N.A.	Investigative	[6]
Ac-I[CV(1Nal)QDWGAHRC]T	DMJVRPD	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(2Igl)QDWGAHRC]T	DM14DEL	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(2Igl)QDWGAHRC]T-NH2	DMQISG6	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(2Nal)QDWGAHRC]T	DM20PEO	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(2Nal)QDWGAHRC]T-NH2	DMX2IRY	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Bpa)QDWGAHRC]T	DMDFKU3	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Bpa)QDWGAHRC]T-NH2	DMZG46O	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Bta)QDWGAHRC]T	DM5NMVP	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Bta)QDWGAHRC]T-NH2	DMFLA5T	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Dht)QDWGAHRC]T	DMO9VWH	Discovery agent	N.A.	Investigative	[7]
Ac-I[CV(Yphs)QDWGAHRC]I-NH2	DMY18ET	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVFQDWGHHRC]T-NH2	DMFOTYQ	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVHQDWGHHRC]T-NH2	DMLU3PZ	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVSQDWGHHRC]T-NH2	DMDPSBQ	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVTQDWGHHRC]T-NH2	DMNVMB5	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVVQDWGAHRC]T-NH2	DMRSKIY	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVWQDWG(Abu)HRC]T-NH2	DMUW3T4	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVWQDWGAHRC]dT	DML5ZSJ	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVWQDWGAHRC]T	DMV3PC7	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVWQDWGHHRC]T-NH2	DMBA1LS	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVWQDWGWHRC]T-NH2	DMDIUK6	Discovery agent	N.A.	Investigative	[7]
Ac-I[CVYQDWGAHRC]T-NH2	DM3Q5SU	Discovery agent	N.A.	Investigative	[7]
Cysteine Sulfenic Acid	DM4GZUJ	N. A.	N. A.	Investigative	[8]

References

• [1] Anti-ageing pipeline starts to mature.Nat Rev Drug Discov. 2018 Sep;17(9):609-612.
• [2] National Cancer Institute Drug Dictionary (drug id 599816).
• [3] The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020 Jun;215:108450.
• [4] Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621: Phase 1 Dose-Escalation Study Results. Am J Ophthalmol. 2022 Mar;235:131-142.
• [5] Compstatin: A Complement Inhibitor on its Way to Clinical Application. Adv Exp Med Biol. 2008; 632: 273-292.
• [6] Hydrophobic effect and hydrogen bonds account for the improved activity of a complement inhibitor, compstatin. J Med Chem. 2006 Jul 27;49(15):4616-22.
• [7] Design and NMR characterization of active analogues of compstatin containing non-natural amino acids. J Med Chem. 2005 Jan 13;48(1):274-86.
• [8] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.