Metformin hydrochloride
Highest phase reached
Approved
Drug type
Small molecule
First approval year
1995
- First approval year
- 1995
- Listing at source
- Listed
- Highest phase reached
- Approved
- Drug type
- Small molecule
- Drug name
- Metformin hydrochloride
- Molecular weight
- 165.63
- Structure (SMILES)
- CN(C)C(=N)NC(=N)N.Cl
- bolamyn sr
- Bolamyn sr
- diagemet xl
- Diagemet xl
- fortamet
- Fortamet
- glucamet 500
- Glucamet 500
- glucamet 850
- Glucamet 850
- glucient sr
- Glucient sr
- glucophage
- Glucophage
- glucophage sr
- Glucophage sr
- glucophage xr
- Glucophage xr
- glumetza
- Glumetza
- glyformin
- Glyformin
- ledermetin
- Ledermetin
- metabet sr
And 49 more, listed on the interactive page.
- 2 x 500 mg Metformin (Glumetza)
- 2 x 500 mg metformin glumetza
- 2x500 mg Metformin (Glumetza)
- 3x500 mg Metformin (Glumetza)
- 500 mg Glucophage XR®
- actoplus met component metformin hydrochloride
- ACTOPLUS MET COMPONENT METFORMIN HYDROCHLORIDE
- apophage
- Apophage
- benofomin
- Benofomin
- diabefagos
- Diabefagos
- diabex
- Diabex
- ex 404
- EX-404
- ex404
- EX404
- glucaminol
- Glucaminol
- Glucophage
- Glucophage 1000 mg
- Glucophage 1000mg
- Glucophage 500mg
And 78 more, listed on the interactive page.
- CAS registry numbers
- 1115-70-4
- ChEMBL ID
- CHEMBL1703
- InChIKey
- OETHQSJEHLVLGH-UHFFFAOYSA-N
- RxNorm IDs (RxCUI)
- 235743
- FDA ingredient codes (UNII)
- 786Z46389E
- 14219
- 43833340
- 53630812
- 137346479
- 137704554
- 176517462
- Applicant
- RANBAXY
- Approval date
- 11 Sept 2003
- Application number
- NDA021591
- Patents
- 1
- Designations
- 1
- Earliest recorded loss of exclusivity
- 1 May 2035
- First in class
- No
- Fast track
- No
- Breakthrough designation
- No
- Orphan designation
- No
- Priority review
- Yes
- Orphan exclusivity
- No
- Accelerated approval
- No
- Availability
- Prescription only
- Boxed warning
- Yes
- Drug name stem
- -formin
Administration routes
- Oral
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O00217
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O00483
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O14561
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O15239
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43181
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43674
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43676
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43677
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43678
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O43920
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O75251
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O75306
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O75380
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O75438
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O75489
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95139
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95167
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95168
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95169
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95178
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95182
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95298
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O95299
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- O96000
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Protein identifier
- P03886
And 26 more, listed on the interactive page.
- Mechanism
- Mitochondrial complex I (NADH dehydrogenase) inhibitor
- Action type
- Inhibitor
- Target
- Mitochondrial complex I (NADH dehydrogenase)
- Mechanism
- Mitochondrial glycerol-3-phosphate dehydrogenase inhibitor
- Action type
- Inhibitor
- Target
- Glycerol-3-phosphate dehydrogenase, mitochondrial
- Condition
- Metabolic Syndrome
- Highest recorded phase
- 3
- Condition identifier
- EFO:0000195
- Subject identifier
- D024821
- Condition
- Squamous Cell Carcinoma of Head and Neck
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000199
- Subject identifier
- D000077195
- Condition
- Adenocarcinoma, Clear Cell
- Highest recorded phase
- 1
- Condition identifier
- EFO:0000348
- Subject identifier
- D018262
- Condition
- Diabetes Mellitus
- Highest recorded phase
- 4
- Condition identifier
- EFO:0000400
- Subject identifier
- D003920
- Condition
- Carcinoma, Intraductal, Noninfiltrating
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000432
- Subject identifier
- D002285
- Condition
- Carcinoma, Endometrioid
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000466
- Subject identifier
- D018269
- Condition
- Glioblastoma
- Highest recorded phase
- 1
- Condition identifier
- EFO:0000519
- Subject identifier
- D005909
- Condition
- Infertility
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000545
- Subject identifier
- D007246
- Condition
- Adenocarcinoma of Lung
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000571
- Subject identifier
- D000077192
- Condition
- Neoplasms
- Highest recorded phase
- 1
- Condition identifier
- EFO:0000616
- Subject identifier
- D009369
- Condition
- Polycystic Ovary Syndrome
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000660
- Subject identifier
- D011085
- Condition
- Prostatic Neoplasms
- Highest recorded phase
- 2
- Condition identifier
- EFO:0000673
- Subject identifier
- D011471
- Condition
- Lung Neoplasms
- Highest recorded phase
- 2
- Condition identifier
- EFO:0001071
- Subject identifier
- D008175
- Condition
- Obesity
- Highest recorded phase
- 2
- Condition identifier
- EFO:0001073
- Subject identifier
- D009765
- Condition
- Ovarian Neoplasms
- Highest recorded phase
- 2
- Condition identifier
- EFO:0001075
- Subject identifier
- D010051
- Condition
- Multiple Myeloma
- Highest recorded phase
- 1
- Condition identifier
- EFO:0001378
- Subject identifier
- D009101
- Condition
- Prostatic Neoplasms
- Highest recorded phase
- 2
- Condition identifier
- EFO:0001663
- Subject identifier
- D011471
- Condition
- Glucose Intolerance
- Highest recorded phase
- 3
- Condition identifier
- EFO:0002546
- Subject identifier
- D018149
- Condition
- Pancreatic Neoplasms
- Highest recorded phase
- 1
- Condition identifier
- EFO:0002618
- Subject identifier
- D010190
- Condition
- Carcinoma, Non-Small-Cell Lung
- Highest recorded phase
- 3
- Condition identifier
- EFO:0003060
- Subject identifier
- D002289
- Condition
- Heart Failure
- Highest recorded phase
- 2
- Condition identifier
- EFO:0003144
- Subject identifier
- D006333
- Condition
- Mouth Neoplasms
- Highest recorded phase
- 3
- Condition identifier
- EFO:0003868
- Subject identifier
- D009062
- Condition
- Renal Insufficiency, Chronic
- Highest recorded phase
- 3
- Condition identifier
- EFO:0003884
- Subject identifier
- D051436
- Condition
- Vitiligo
- Highest recorded phase
- 2
- Condition identifier
- EFO:0004208
- Subject identifier
- D014820
- Condition
- Aortic Aneurysm, Abdominal
- Highest recorded phase
- 2
- Condition identifier
- EFO:0004214
- Subject identifier
- D017544
And 29 more, listed on the interactive page.
- Condition identifier
- EFO_0000195
- Highest recorded phase
- 3
- Condition identifier
- EFO_0000199
- Highest recorded phase
- 2
- Condition identifier
- EFO_0000348
- Condition identifier
- EFO_0000400
- Condition identifier
- EFO_0000545
- Highest recorded phase
- 2
- Condition identifier
- EFO_0000616
- Highest recorded phase
- 1
- Condition identifier
- EFO_0000660
- Highest recorded phase
- 3
- Condition identifier
- EFO_0000673
- Highest recorded phase
- 2
- Condition identifier
- EFO_0001071
- Highest recorded phase
- 2
- Condition identifier
- EFO_0001073
- Highest recorded phase
- 3
- Condition identifier
- EFO_0001378
- Highest recorded phase
- 1
- Condition identifier
- EFO_0002546
- Highest recorded phase
- 3
- Condition identifier
- EFO_0002618
- Highest recorded phase
- 1
- Condition identifier
- EFO_0003060
- Highest recorded phase
- 3
- Condition identifier
- EFO_0003144
- Highest recorded phase
- 2
- Condition identifier
- EFO_0003868
- Highest recorded phase
- 3
- Condition identifier
- EFO_0003884
- Highest recorded phase
- 3
- Condition identifier
- EFO_0004208
- Highest recorded phase
- 2
- Condition identifier
- EFO_0004214
- Condition identifier
- EFO_0004593
- Highest recorded phase
- 3
- Condition identifier
- EFO_0004616
- Condition identifier
- EFO_0006859
- Condition identifier
- EFO_0008520
- Highest recorded phase
- 2
- Condition identifier
- EFO_0008522
- Highest recorded phase
- 2
- Condition identifier
- EFO_0022597
- Highest recorded phase
- 3
And 53 more, listed on the interactive page.
- Warning
- Black Box Warning
- Effect
- cardiotoxicity
- Warning
- Black Box Warning
- Effect
- metabolic toxicity
- Warning
- Black Box Warning
- Effect
- respiratory toxicity
- Warning
- Black Box Warning
- Effect
- vascular toxicity
- Warning
- Black Box Warning
- Effect
- cardiotoxicity
- Country
- United States
- Warning
- Black Box Warning
- Effect
- metabolic toxicity
- Country
- United States
- Warning
- Black Box Warning
- Effect
- respiratory toxicity
- Country
- United States
- Warning
- Black Box Warning
- Effect
- vascular toxicity
- Country
- United States
- Event
- acute kidney injury
- Reports
- 5,353
- Reporting signal score
- 8,975.62
- Event
- anuria
- Reports
- 479
- Reporting signal score
- 949.981
- Event
- blood glucose increased
- Reports
- 1,324
- Reporting signal score
- 1,431.6
- Event
- blood lactic acid increased
- Reports
- 341
- Reporting signal score
- 723.886
- Event
- dehydration
- Reports
- 1,124
- Reporting signal score
- 555.703
- Event
- diabetes mellitus inadequate control
- Reports
- 852
- Reporting signal score
- 1,820.93
- Event
- diabetic ketoacidosis
- Reports
- 970
- Reporting signal score
- 1,468.92
- Event
- diabetic metabolic decompensation
- Reports
- 237
- Reporting signal score
- 699.426
- Event
- diarrhoea
- Reports
- 3,276
- Reporting signal score
- 919.044
- Event
- euglycaemic diabetic ketoacidosis
- Reports
- 330
- Reporting signal score
- 737.463
- Event
- glycosylated haemoglobin increased
- Reports
- 574
- Reporting signal score
- 981.004
- Event
- haemodialysis
- Reports
- 371
- Reporting signal score
- 579.065
- Event
- hyperglycaemia
- Reports
- 868
- Reporting signal score
- 1,105.51
- Event
- hyperkalaemia
- Reports
- 1,542
- Reporting signal score
- 2,511.56
- Event
- hyperlactacidaemia
- Reports
- 426
- Reporting signal score
- 1,231.31
- Event
- hypoglycaemia
- Reports
- 3,075
- Reporting signal score
- 6,479.05
- Event
- hypoglycaemic coma
- Reports
- 394
- Reporting signal score
- 1,028.87
- Event
- hypotension
- Reports
- 1,691
- Reporting signal score
- 674.675
- Event
- hypothermia
- Reports
- 426
- Reporting signal score
- 662.12
- Event
- ketoacidosis
- Reports
- 412
- Reporting signal score
- 844.539
- Event
- lactic acidosis
- Reports
- 8,664
- Reporting signal score
- 30,366
- Event
- metabolic acidosis
- Reports
- 2,668
- Reporting signal score
- 6,468.23
- Event
- pancreatitis acute
- Reports
- 574
- Reporting signal score
- 590.711
- Event
- pemphigoid
- Reports
- 442
- Reporting signal score
- 829.48
- Event
- renal failure
- Reports
- 1,448
- Reporting signal score
- 1,305.47
And 6 more, listed on the interactive page.
- NCT00005669
- NCT00209482
- NCT03051451
- NCT00035542
- NCT00035568
- NCT00290940
- NCT00449930
- NCT00482729
- NCT00499707
- NCT00532935
- NCT00541450
- NCT00612144
- NCT00660907
- NCT00680745
- NCT00830076
- NCT00859898
- NCT00865033
- NCT00882882
- NCT00897390
- NCT00929201
- NCT00961480
- NCT00961857
- NCT01002807
- NCT01269996
- NCT01386671
And 83 more, listed on the interactive page.
- Dose
- 50 mg sitagliptin and 500 mg metformin HCl
- Route
- Oral
- How often
- Twice daily
Conditions of use
- Do not split or divide tablets
- Hydrogen bond acceptors
- 2
- Hydrogen bond donors
- 4
- Polar surface area
- 88.99
- Calculated partition coefficient (ALogP)
- -1.03
- Prodrug
- No
- Chirality
- Achiral
- Inorganic
- No
- Rule-of-five violations
- 0
- Rotatable bonds
- 0
- Heavy atoms
- 10
- Molecular formula
- C4H12ClN5
- Monoisotopic mass
- 165.0781231
- Natural product
- No
- 0006-0078
- 0006-0080
- 0006-0081
- 0006-0575
- 0006-0577
- 0006-5369
- 0006-5370
- 0006-5373
- 0006-5374
- 0093-7455
- 0093-7456
- 0093-7457
- 0310-6225
- 0310-6250
- 0310-6260
- 0310-6270
- 0310-6280
- 0378-6001
- 0378-6002
- 0378-7185
- 0378-7186
- 0378-7187
- 0378-8175
- 0378-8176
- 0378-8177
And 595 more, listed on the interactive page.
- Recorded assays
- 1,468
- Active assays
- 9
- Confirmatory
- Other
- Screening
- Summary
- Hypoglycemic Agents
Distribution coefficient (LogD)
- Median
- -6.13
- Mean
- -6.13
- Minimum
- -6.13
- Maximum
- -6.13
- Unit
- unitless
- Assays
- 1
- Standard deviation
- 0
- Summary method
- median
- Censored results excluded
- 0
- Other units excluded
- 0
- Unknown units excluded
- 0
Measurement types
- LogD
Oral bioavailability
- Median
- 59
- Mean
- 58
- Minimum
- 50
- Maximum
- 64
- Unit
- %
- Assays
- 4
- Standard deviation
- 5.83095
- Summary method
- median
- Censored results excluded
- 0
- Other units excluded
- 0
- Unknown units excluded
- 0
Measurement types
- F
Related records
Trials (2,082)
- "Hepatic Substrate Flux Rates in Type 2 Diabetes"
- "MetCool ACS"- Metformin "Cooling" Effect on Metformin-naive Patients Treated With PCI Because of Acute Coronary Syndrome
- 1% Metformin Gel in the Treatment of Class II Furcation Defects
- 1% Metformin in Moderate and Severe Periodontitis
- 12 Weeks Treatment With 3 Different Doses of BI 10773 in Type 2 Diabetic Patients
- 24-Hour Glycemia: Rosiglitazone Versus Glimepiride In Type 2 Diabetes
- 24-week Study Comparing Lixisenatide to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 Years
- 24-week Treatment With Lixisenatide in Type 2 Diabetes Insufficiently Controlled With Metformin and Insulin Glargine
- 30-Week Extension to an Initial Combination Study (24 Weeks in Duration) of Sitagliptin With Pioglitazone (0431-064)
- 52-week add-on to Metformin Comparison of Saxagliptin and Sulphonylurea, With a 52-week Extension Period
- A 12 Week Study in Patients With Type 2 Diabetes Mellitus (T2DM)
- A 24-week Open-Label, Phase 3b Trial With a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin Compared to Insulin Glargine in Subjects withType 2 Diabetes Who Have Glycemic Control on Metformin
- A Bioequivalence Study of CT-L01 Compared to Co-administration (ALO 12.5 mg and MET XR 500 mg) in Healthy Volunteers
- A Bioequivalence Study of CT-L01 Compared to Co-administration (ALO 25 mg and MET XR 1,000 mg) in Healthy Volunteers
- A Bioequivalence Study Of Ethinylestradiol + Gestodene In Female And Healthy Volunteers.
- A Bioequivalence Study of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) With Respect to the Individual Components
- A Bioequivalence Study of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) With Respect to the Individual Components
- A Bioequivalence Study of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) With Respect to the Individual Components in Healthy Fed Participants
- A Bioequivalence Study of the Fixed Dose Combination Tablets of Canagliflozin and Metformin Extended Release (XR) With Respect to the Individual Components in Healthy Fed Participants
- A Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration
Approved for (2)
In development for (48)
- Abdominal aortic aneurysm Phase 2
- Brain ischemia Phase 1
- Breast cancer Phase 3
- Chronic kidney disease Phase 3
- Clear cell adenocarcinoma Phase 1
- Diabetic neuropathy Phase 1
- Ductal breast carcinoma in situ Phase 2
- Endometrial carcinoma Phase 2
- Endometrioid adenocarcinoma Phase 2
- Exocrine pancreatic carcinoma Phase 1
- Fallopian tube cancer Phase 2
- Fanconi anemia Phase 2
- Gestational diabetes Phase 3
- Glioblastoma Phase 1
- Gliosarcoma Phase 1
- Glucose intolerance Phase 3
- Head and neck cancer Early phase 1
- Heart failure Phase 2
- Hyperinsulinism Phase 2
- Infertility disorder Phase 2
Other linked conditions (2)
- Osteoarthritis
- Precocious puberty
Targets (51)
- COXFA4 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- COXFA4L2 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- GPD2 Mitochondrial glycerol-3-phosphate dehydrogenase inhibitor
- MT-ND1 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND2 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND3 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND4 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND4L Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND5 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- MT-ND6 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA1 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA10 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA11 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA12 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA13 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA2 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA3 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA5 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA6 Mitochondrial complex I (NADH dehydrogenase) inhibitor
- NDUFA7 Mitochondrial complex I (NADH dehydrogenase) inhibitor