pembrolizumab Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
humanized origin 4924 1374853-91-4

Description:

MoleculeDescription

Synonyms:

  • pembrolizumab
  • keytruda
  • lambrolizumab
  • SCH-900475
  • MK-3475
A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity.
  • Molecular weight:
  • Formula:
  • CLOGP:
  • LIPINSKI: None
  • HAC: None
  • HDO: None
  • TPSA:
  • ALOGS:
  • ROTB: None

Drug dosage:

None

ADMET properties:

None

Approvals:

DateAgencyCompanyOrphan
July 17, 2015 EMA Merck Sharp & Dohme Limited
Sept. 4, 2014 FDA MERCK SHARP DOHME

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 1971.27 38.62 453 2818 11675 2343139
Product use in unapproved indication 724.77 38.62 202 3069 10998 2343816
Immune-mediated adverse reaction 578.40 38.62 81 3190 44 2354770
Product use issue 489.03 38.62 152 3119 12017 2342797
Pneumonitis 413.22 38.62 105 3166 3934 2350880
Death 371.10 38.62 215 3056 81253 2273561
Pyrexia 230.67 38.62 137 3134 53571 2301243
Hypothyroidism 222.56 38.62 66 3205 4391 2350423
Adverse event 218.53 38.62 74 3197 7585 2347229
Colitis 216.42 38.62 67 3204 5159 2349655
Fatigue 211.68 38.62 154 3117 84719 2270095
Off label use 188.86 38.62 136 3135 73462 2281352
Autoimmune colitis 168.95 38.62 27 3244 73 2354741
Diarrhoea 158.36 38.62 129 3142 83435 2271379
Rash 156.95 38.62 112 3159 59446 2295368
Pneumonia 137.37 38.62 96 3175 49200 2305614
Nausea 133.02 38.62 133 3138 112056 2242758
Adrenal insufficiency 131.14 38.62 34 3237 1366 2353448
Acute kidney injury 128.76 38.62 75 3196 28047 2326767
Autoimmune hypothyroidism 126.53 38.62 19 3252 28 2354786
Autoimmune hepatitis 120.05 38.62 33 3238 1662 2353152
Tubulointerstitial nephritis 116.79 38.62 35 3236 2403 2352411
Hepatitis 115.54 38.62 44 3227 6293 2348521
Hypophysitis 114.19 38.62 22 3249 215 2354599
Dyspnoea 111.30 38.62 103 3168 78630 2276184
Hyperthyroidism 108.69 38.62 32 3239 2065 2352749
Autoimmune thyroiditis 104.55 38.62 24 3247 573 2354241
Fulminant type 1 diabetes mellitus 102.07 38.62 17 3254 64 2354750
Tumour pseudoprogression 100.43 38.62 16 3255 42 2354772
Vomiting 99.82 38.62 93 3178 71509 2283305
Pleural effusion 98.77 38.62 47 3224 11621 2343193
Aspartate aminotransferase increased 98.28 38.62 48 3223 12564 2342250
Decreased appetite 93.92 38.62 62 3209 28829 2325985
Myocarditis 92.12 38.62 25 3246 1198 2353616
Inappropriate schedule of product administration 90.77 38.62 45 3226 12159 2342655
Interstitial lung disease 89.93 38.62 39 3232 7773 2347041
Asthenia 89.62 38.62 73 3198 46853 2307961
Vitiligo 88.57 38.62 18 3253 236 2354578
Thyroiditis 86.74 38.62 19 3252 364 2354450
Type 1 diabetes mellitus 86.72 38.62 21 3250 635 2354179
Myositis 85.38 38.62 24 3247 1311 2353503
Alanine aminotransferase increased 84.83 38.62 45 3226 13987 2340827
Nephritis 83.98 38.62 19 3252 424 2354390
Pulmonary embolism 79.39 38.62 47 3224 18036 2336778
Respiratory failure 77.88 38.62 42 3229 13486 2341328
Myasthenia gravis 77.57 38.62 19 3252 603 2354211
Uveitis 76.67 38.62 23 3248 1582 2353232
Anaemia 74.64 38.62 58 3213 34734 2320080
Neutropenia 74.26 38.62 48 3223 21500 2333314
Pericardial effusion 73.62 38.62 28 3243 3981 2350833
Constipation 71.64 38.62 47 3224 21582 2333232
Weight decreased 69.02 38.62 51 3220 28320 2326494
Autoimmune arthritis 66.08 38.62 10 3261 16 2354798
Lichenoid keratosis 65.99 38.62 15 3256 342 2354472
Therapy partial responder 64.40 38.62 15 3256 382 2354432
Autoimmune nephritis 64.33 38.62 10 3261 21 2354793
Hepatocellular injury 62.69 38.62 25 3246 4030 2350784
Abdominal pain 62.43 38.62 52 3219 34322 2320492
Diabetic ketoacidosis 62.24 38.62 24 3247 3540 2351274
Hyponatraemia 62.05 38.62 36 3235 13289 2341525
Thrombocytopenia 61.94 38.62 41 3230 19090 2335724
Arthralgia 59.59 38.62 62 3209 54223 2300591
Hepatic function abnormal 59.13 38.62 27 3244 6065 2348749
Neuropathy peripheral 58.90 38.62 33 3238 11399 2343415
Cholestasis 57.73 38.62 23 3248 3698 2351116
Metastases to central nervous system 54.31 38.62 19 3252 2129 2352685
Adrenocorticotropic hormone deficiency 54.21 38.62 9 3262 33 2354781
Back pain 51.55 38.62 45 3226 31614 2323200
Sjogren's syndrome 50.35 38.62 15 3256 1006 2353808
General physical health deterioration 49.91 38.62 32 3239 14107 2340707
Cardiac failure 49.31 38.62 30 3241 12064 2342750
Cough 47.84 38.62 44 3227 33073 2321741
Immune-mediated hepatitis 47.25 38.62 8 3263 34 2354780
Polymyalgia rheumatica 46.54 38.62 12 3259 470 2354344
Hypopituitarism 46.38 38.62 10 3261 177 2354637
Myalgia 45.89 38.62 37 3234 23296 2331518
Metastatic malignant melanoma 45.85 38.62 11 3260 319 2354495
Pain 44.77 38.62 57 3214 61800 2293014
Stomatitis 44.56 38.62 26 3245 9684 2345130
Immune-mediated enterocolitis 42.76 38.62 7 3264 23 2354791
Sepsis 42.15 38.62 32 3239 18456 2336358
Febrile neutropenia 41.82 38.62 26 3245 10856 2343958
Rash maculo-papular 41.74 38.62 19 3252 4233 2350581
Renal failure 41.71 38.62 31 3240 17318 2337496
Malaise 41.44 38.62 52 3219 55533 2299281
Pruritus 41.34 38.62 46 3225 43294 2311520
Dehydration 40.99 38.62 34 3237 22261 2332553
Lung disorder 40.56 38.62 21 3250 6191 2348623
Chills 40.12 38.62 29 3242 15523 2339291
Autoimmune pancreatitis 38.78 38.62 7 3264 46 2354768

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 2637.80 39.36 699 4004 13459 1728619
Immune-mediated adverse reaction 1039.29 39.36 160 4543 39 1742039
Product use in unapproved indication 720.21 39.36 236 4467 9186 1732892
Pneumonitis 573.32 39.36 162 4541 3753 1738325
Product use issue 521.01 39.36 181 4522 8390 1733688
Interstitial lung disease 499.18 39.36 181 4522 9515 1732563
Death 382.89 39.36 314 4389 87129 1654949
Adverse event 300.08 39.36 103 4600 4565 1737513
Colitis 283.38 39.36 96 4607 4084 1737994
Pyrexia 247.32 39.36 188 4515 46212 1695866
Fatigue 245.18 39.36 194 4509 50587 1691491
Hypothyroidism 243.36 39.36 76 4627 2484 1739594
Off label use 243.13 39.36 173 4530 38398 1703680
Adrenal insufficiency 238.40 39.36 65 4638 1300 1740778
Diarrhoea 218.45 39.36 186 4517 53666 1688412
Rash 182.32 39.36 146 4557 38547 1703531
Type 1 diabetes mellitus 180.26 39.36 47 4656 785 1741293
Myasthenia gravis 174.28 39.36 43 4660 568 1741510
Autoimmune colitis 167.06 39.36 33 4670 137 1741941
Hypophysitis 165.43 39.36 38 4665 361 1741717
Pneumonia 161.77 39.36 147 4556 46035 1696043
Decreased appetite 161.36 39.36 112 4591 23759 1718319
Dyspnoea 156.12 39.36 152 4551 51907 1690171
Autoimmune hepatitis 148.08 39.36 39 4664 678 1741400
Myocarditis 145.87 39.36 48 4655 1855 1740223
Myositis 141.47 39.36 45 4658 1558 1740520
Immune-mediated hepatitis 138.74 39.36 25 4678 54 1742024
Tumour pseudoprogression 130.20 39.36 23 4680 42 1742036
Asthenia 122.39 39.36 111 4592 34559 1707519
Vitiligo 118.92 39.36 27 4676 242 1741836
Hyperthyroidism 117.60 39.36 39 4664 1543 1740535
Respiratory failure 111.99 39.36 74 4629 14431 1727647
Therapy partial responder 109.53 39.36 26 4677 288 1741790
Arthralgia 109.06 39.36 88 4615 23356 1718722
Acute kidney injury 108.12 39.36 104 4599 34840 1707238
Organising pneumonia 108.08 39.36 32 4671 866 1741212
Pruritus 105.55 39.36 86 4617 23136 1718942
Pemphigoid 104.50 39.36 33 4670 1114 1740964
Hepatitis 98.25 39.36 47 4656 4908 1737170
Pleural effusion 93.85 39.36 60 4643 11050 1731028
Sjogren's syndrome 90.32 39.36 20 4683 158 1741920
Thyroiditis 88.90 39.36 23 4680 371 1741707
Hepatic function abnormal 87.89 39.36 49 4654 7025 1735053
Tubulointerstitial nephritis 87.12 39.36 37 4666 2921 1739157
Nausea 81.79 39.36 108 4595 51088 1690990
Nephritis 81.51 39.36 22 4681 421 1741657
Pneumonia bacterial 75.20 39.36 26 4677 1168 1740910
Diabetic ketoacidosis 73.88 39.36 34 4669 3249 1738829
Pulmonary embolism 73.63 39.36 55 4648 13004 1729074
Liver disorder 69.88 39.36 39 4664 5597 1736481
Hypopituitarism 67.29 39.36 17 4686 248 1741830
Autoimmune thyroiditis 67.16 39.36 17 4686 250 1741828
Sepsis 65.97 39.36 61 4642 19377 1722701
Weight decreased 65.13 39.36 65 4638 22688 1719390
Lung disorder 65.04 39.36 36 4667 5083 1736995
Autoimmune hypothyroidism 64.65 39.36 11 4692 14 1742064
Malaise 64.34 39.36 73 4630 29492 1712586
Polymyalgia rheumatica 63.88 39.36 16 4687 225 1741853
Metastatic malignant melanoma 63.18 39.36 18 4685 423 1741655
Hyponatraemia 60.05 39.36 42 4661 8958 1733120
Thrombocytopenia 59.50 39.36 60 4643 21189 1720889
Hepatic enzyme increased 58.96 39.36 37 4666 6584 1735494
General physical health deterioration 58.25 39.36 48 4655 13070 1729008
Adrenocorticotropic hormone deficiency 57.79 39.36 12 4691 67 1742011
Cancer pain 57.69 39.36 16 4687 340 1741738
Inappropriate schedule of product administration 57.34 39.36 38 4665 7421 1734657
Lichenoid keratosis 55.76 39.36 16 4687 386 1741692
Autoimmune myocarditis 54.18 39.36 10 4693 26 1742052
Cough 53.36 39.36 54 4649 19143 1722935
Pain 53.24 39.36 63 4640 26594 1715484
Anaemia 51.35 39.36 65 4638 29392 1712686
Fulminant type 1 diabetes mellitus 50.78 39.36 12 4691 130 1741948
Autoimmune arthritis 50.74 39.36 9 4694 17 1742061
Constipation 48.79 39.36 46 4657 14954 1727124
Muscular weakness 48.64 39.36 39 4664 10210 1731868
Immune-mediated pneumonitis 47.09 39.36 8 4695 10 1742068
Confusional state 47.02 39.36 53 4650 21225 1720853
Encephalitis 46.44 39.36 18 4685 1120 1740958
Immune-mediated enterocolitis 45.81 39.36 9 4694 36 1742042
Autoimmune nephritis 45.42 39.36 9 4694 38 1742040
Drug-induced liver injury 44.52 39.36 24 4679 3213 1738865
Diabetes mellitus 43.20 39.36 31 4672 6877 1735201
Dermatitis 42.58 39.36 19 4684 1687 1740391
Infection 42.29 39.36 39 4664 12321 1729757
Haemophagocytic lymphohistiocytosis 42.10 39.36 18 4685 1442 1740636
Pancreatitis 42.10 39.36 31 4672 7156 1734922
Liver function test increased 41.18 39.36 18 4685 1521 1740557
Aspartate aminotransferase increased 40.86 39.36 36 4667 10720 1731358
Alanine aminotransferase increased 40.58 39.36 38 4665 12240 1729838
Pulmonary sarcoidosis 39.70 39.36 10 4693 144 1741934

Pharmacologic Action:

SourceCodeDescription
ATC L01XC18 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Monoclonal antibodies
FDA EPC N0000191260 Programmed Death Receptor-1 Blocking Antibody
FDA MoA N0000191259 Programmed Death Receptor-1-directed Antibody Interactions
MeSH PA D000970 Antineoplastic Agents
MeSH PA D000074322 Antineoplastic Agents, Immunological

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
Metastatic malignant melanoma indication 443493003

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Programmed cell death protein 1 Membrane receptor ANTIBODY BINDING Kd 10 IUPHAR DRUG LABEL

External reference:

IDSource
D10574 KEGG_DRUG
4033703 VUID
N0000191088 NUI
C3658706 UMLSCUI
763541003 SNOMEDCT_US
1547545 RXNORM
015666 NDDF
30533 MMSL
d08287 MMSL
4033703 VANDF
716125002 SNOMEDCT_US
DPT0O3T46P UNII
9798 INN_ID
DB09037 DRUGBANK_ID
CHEMBL3137343 ChEMBL_ID
7499 IUPHAR_LIGAND_ID
C582435 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
KEYTRUDA HUMAN PRESCRIPTION DRUG LABEL 1 0006-3026 INJECTION, SOLUTION 25 mg INTRAVENOUS BLA 17 sections
KEYTRUDA HUMAN PRESCRIPTION DRUG LABEL 1 0006-3029 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS BLA 17 sections