Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Programmed cell death protein 1 (PD-1)
• Synonyms: hPD1; hPD-1; Protein PD1; Protein PD-1; PD1; CD279
• Gene Name: PDCD1
• DTT Type: Successful target; [1]
• BioChemical Class: Immunoglobulin
• UniProt ID: PDCD1_HUMAN
• TTD ID: T59631
• Sequence:
  MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTS
  ESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGT
  YLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGS
  LVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVP
  CVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL
• Function: Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta. Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self.
• KEGG Pathway:
  Cell adhesion molecules (CAMs) (hsa04514)
  T cell receptor signaling pathway (hsa04660)
• Reactome Pathway: PD-1 signaling (R-HSA-389948)

Molecular Interaction Atlas (MIA) of This DTT

9 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cemiplimab	DMKMJHE	Cutaneous squamous cell carcinoma	2C30	Approved	[2]
Dostarlimab	DM78NWP	Endometrial cancer	2C76	Approved	[3]
MK-3475	DMBYNW0	Melanoma	2C30	Approved	[1]
Nivolumab	DMAB9QE	Melanoma	2C30	Approved	[1]
Pembrolizumab	DMFQEA6	Melanoma	2C30	Approved	[4]
Retifanlimab	DMRKTCP	Neuroendocrine cancer	2B72.1	Approved	[5]
Sintilimab	DMGWR0C	Hodgkin lymphoma	2B30	Approved	[6]
Tislelizumab	DMGVUO5	Hodgkin lymphoma	2B30	Approved	[7]
Toripalimab	DMSGA6Z	Demodex blepharitis	1G07	Approved in China	[8]

49 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AK04	DMU7K86	Actinic keratosis	EK90.0	Phase 3	[9]
Balstilimab	DM5ARDP	Cervical cancer	2C77.0	Phase 3	[10]
BGB-A317	DM7NJYC	Hepatocellular carcinoma	2C12.02	Phase 3	[5]
CS-1003	DM5XGM9	Hepatocellular carcinoma	2C12.02	Phase 3	[11]
IBI-308	DM5KL8E	Bronchioalveolar carcinoma	2C25.0	Phase 3	[4]
INCSHR1210	DMZA2K0	Bronchioalveolar carcinoma	2C25.0	Phase 3	[5]
Nofazinlimab	DMST5HF	Liver cancer	2C12	Phase 3	[12]
PDR001	DM53J6B	Melanoma	2C30	Phase 3	[13]
Sasanlimab	DMUVSG4	Non-muscle invasive bladder cancer	2C94	Phase 3	[14]
Spartalizumab	DM4TOEQ	Melanoma	2C30	Phase 3	[4]
AGEN2034	DMPO7UG	Cervical cancer	2C77.0	Phase 2	[5]
AK104	DMXJ8Z4	Cervical cancer	2C77.0	Phase 2	[15]
AZD7789	DMOIHWI	Hodgkin lymphoma	2B30	Phase 2	[16]
JNJ 63723283	DMBXWJ5	Ulcerative colitis	DD71	Phase 2	[4]
JTX-4014	DMOT0M7	Non-small-cell lung cancer	2C25.Y	Phase 2	[17]
Lorigerlimab	DM2E8Z5	Prostate cancer	2C82.0	Phase 2	[18]
M7824	DMJCULI	Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
Peresolimab	DMYT8E0	Rheumatoid arthritis	FA20	Phase 2	[19]
RO7121661	DM8A120	Esophageal squamous cell carcinoma	2E60.1	Phase 2	[20]
SAR445877	DM91KZL	Aggressive cancer	2A00-2F9Z	Phase 2	[21]
Vudalimab	DMSEEI0	Prostate cancer	2C82.0	Phase 2	[22]
Cetrelimab	DMJBQ96	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[23]
MGD013	DMCVMUL	Hepatocellular carcinoma	2C12.02	Phase 1/2	[4]
Rilvegostomig	DMDWCM2	Non-small-cell lung cancer	2C25	Phase 1/2	[24]
609A	DMOIE05	Solid tumour/cancer	2A00-2F9Z	Phase 1	[25]
ADPT01	DMS6DPF	Breast cancer	2C60-2C65	Phase 1	[26]
AMG 404	DMVQX5K	Solid tumour/cancer	2A00-2F9Z	Phase 1	[27]
AMP-224	DMH9M62	Colorectal cancer	2B91.Z	Phase 1	[28]
APL-501	DM4WAC2	Solid tumour/cancer	2A00-2F9Z	Phase 1	[29]
BI 754091	DMWHZFS	Neoplasm	2A00-2F9Z	Phase 1	[30]
BI-754091	DM3JOIX	Advanced malignancy	2A00-2F9Z	Phase 1	[4]
CBT-501	DMW1OKT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
CC-90006	DMHJLB6	Psoriasis vulgaris	EA90	Phase 1	[13]
CDX-527	DMVDIWO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[31]
GSK2661380	DMAK89L	Solid tumour/cancer	2A00-2F9Z	Phase 1	[32]
IBI318	DMB83V4	Non-small-cell lung cancer	2C25	Phase 1	[33]
LZM009	DMHDCSL	Advanced malignancy	2A00-2F9Z	Phase 1	[4]
MEDI0680	DMPLFBV	Solid tumour/cancer	2A00-2F9Z	Phase 1	[34]
MEDI5752	DMJ1E24	Non-small-cell lung cancer	2C25	Phase 1	[35]
MGD019	DM2BYWI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[36]
PF-06801591	DMDE9I6	Advanced malignancy	2A00-2F9Z	Phase 1	[4]
RG6139	DMJFM3O	Solid tumour/cancer	2A00-2F9Z	Phase 1	[37]
RG6279	DMSM0IJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[38]
SI-B003	DMJW5R0	Solid tumour/cancer	2A00-2F9Z	Phase 1	[39]
Sym021	DMVXLS5	Advanced malignancy	2A00-2F9Z	Phase 1	[4]
SYN125	DM4UVTO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[40]
TSR-042	DM56PFL	Advanced malignancy	2A00-2F9Z	Phase 1	[4]
XmAb20717	DMJIH83	Advanced malignancy	2A00-2F9Z	Phase 1	[41]
XmAb23104	DMK9XUQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[42]

9 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,2,4-oxadiazole derivative 1	DMESOA8	Hepatitis	DB97.Z	Patented	[43]
1,2,4-oxadiazole derivative 2	DMA42SB	Hepatitis	DB97.Z	Patented	[43]
1,3,4-oxadiazole derivative 1	DMJMCNP	Hepatitis	DB97.Z	Patented	[43]
1,3,4-oxadiazole derivative 2	DMH26EO	Hepatitis	DB97.Z	Patented	[43]
Cyclic compound 1	DMSVMUT	Hepatitis	DB97.Z	Patented	[43]
Cyclic compound 2	DMGRBAJ	Hepatitis	DB97.Z	Patented	[43]
Cyclic compound 3	DMVOEN7	Hepatitis	DB97.Z	Patented	[43]
PMID30107136-Compound-Example15	DMYHQ0S	Hepatitis	DB97.Z	Patented	[43]
PMID30107136-Compound-Example16	DM6EKIV	Hepatitis	DB97.Z	Patented	[43]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AUNP-12	DM0KM6F	N. A.	N. A.	Preclinical	[4]

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID30247903-Compound-General structure13	DMJ0YZA	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure14	DM5Z4JR	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure15	DMCJDLO	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure16	DMVR4QH	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure17	DMC3GFI	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure20	DMCNXKE	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure21	DMFACRH	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure22	DMLD1IU	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure23	DMMXLHW	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure24	DM8CPZB	N. A.	N. A.	Investigative	[4]
PMID30247903-Compound-General structure25	DMEMLHR	N. A.	N. A.	Investigative	[4]
YH008	DMTIP9S	Aggressive cancer	2A00-2F9Z	Investigative	[44]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Melanoma	2C82	Skin	7.26E-01	-0.01	-0.03

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