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Compound Detail

CHEMBL442

ERGOTAMINE
💊 Approved Drug
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💊 Approved Drug
CN1C[C@H](C(=O)N[C@]2(C)O[C@@]3(O)[C@@H]4CCCN4C(=O)[C@H](Cc4ccccc4)N3C2=O)C=C2c3cccc4[nH]cc(c34)C[C@H]21

Basic Information

ChEMBL ID CHEMBL442
Name ERGOTAMINE
Phase Approved
Structure Type MOL
InChI Key XCGSFFUVFURLIX-VFGNJEKYSA-N
Therapeutic ✓ Yes

Known Names

Ergotamina Ergotamine NSC-95090
31
Targets
64
Activities
3
Assay Types
7
PK Parameters
20
Publications
3
Known Names
2
Indications

Molecular Properties

581.7
MW (Da)
1.99
ALogP
6
HBA
3
HBD
118.2
PSA (Ų)
0.43
QED
1
Ro5 Violations
4
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1948
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral Topical

Flags

Black Box Warning Withdrawn Natural Product

Extended Properties

Molecular Formula C33H35N5O5
MW 581.67
Aromatic Rings 3
Heavy Atoms 43
NP-Likeness 0.96

Indications

Migraine Disorders Hypotension, Orthostatic

ATC Classification

N02CA02
ergotamine
Level 1: NERVOUS SYSTEM
Level 2: ANALGESICS
N02CA52
ergotamine, combinations excl. psycholeptics
Level 1: NERVOUS SYSTEM
Level 2: ANALGESICS
N02CA72
ergotamine, combinations with psycholeptics
Level 1: NERVOUS SYSTEM
Level 2: ANALGESICS

Activity Summary

Ki 36 meas. best 10.04
IC50 26 meas. best 9.7
EC50 2 meas. best 8.14

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
5-hydroxytryptamine receptor 1B
CHEMBL3459
Ki 10.04 10.04 0.1 1
5-hydroxytryptamine receptor 1B
CHEMBL3459
IC50 9.7 9.7 0.2 1
5-hydroxytryptamine receptor 1A
CHEMBL273
Ki 9.35 9.35 0.4 1
5-hydroxytryptamine receptor 1A
CHEMBL273
IC50 9.11 9.11 0.8 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 9.1 9.1 0.8 1
5-hydroxytryptamine receptor 1D
CHEMBL1983
Ki 9.1 8.586 0.8 5
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 9.02 9.02 0.9 1
D(2) dopamine receptor
CHEMBL217
Ki 8.84 8.84 1.4 1
D(3) dopamine receptor
CHEMBL234
Ki 8.83 8.83 1.5 1
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 8.76 8.76 1.8 1
Alpha-2C adrenergic receptor
CHEMBL1916
Ki 8.74 8.74 1.8 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 8.73 8.73 1.9 1
5-hydroxytryptamine receptor 6
CHEMBL3371
IC50 8.69 8.69 2.0 1
5-hydroxytryptamine receptor 1B
CHEMBL1898
Ki 8.68 8.57 2.1 3
Alpha-2A adrenergic receptor
CHEMBL1867
IC50 8.67 8.67 2.1 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 8.66 8.66 2.2 1
Unchecked
CHEMBL612545
Ki 8.61 8.61 2.4 1
Alpha-1A adrenergic receptor
CHEMBL319
Ki 8.49 8.49 3.3 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
IC50 8.46 8.46 3.5 1
Unchecked
CHEMBL612545
IC50 8.44 8.44 3.6 1
Alpha-2B adrenergic receptor
CHEMBL1942
IC50 8.41 8.41 3.8 1
D(2) dopamine receptor
CHEMBL217
IC50 8.37 8.37 4.3 1
D(3) dopamine receptor
CHEMBL234
IC50 8.37 8.37 4.3 1
Alpha-1B adrenergic receptor
CHEMBL315
Ki 8.34 8.34 4.5 1
5-hydroxytryptamine receptor 2A
CHEMBL224
IC50 8.19 8.19 6.5 1
5-hydroxytryptamine receptor 2A
CHEMBL224
EC50 8.14 8.12 7.3 2
Alpha-1A adrenergic receptor
CHEMBL319
IC50 8.09 8.09 8.1 1
Alpha-1B adrenergic receptor
CHEMBL315
IC50 8.09 8.09 8.2 1
Alpha-2C adrenergic receptor
CHEMBL1916
IC50 7.92 7.92 12.0 1
5-hydroxytryptamine receptor 5A
CHEMBL3426
Ki 7.85 7.704 14.0 5
Alpha-1D adrenergic receptor
CHEMBL223
Ki 7.62 7.62 24.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
Ki 7.54 7.54 29.0 1
Alpha-1D adrenergic receptor
CHEMBL223
IC50 7.31 7.31 49.0 1
5-hydroxytryptamine receptor 2C
CHEMBL225
IC50 7.25 7.25 56.0 1
5-hydroxytryptamine receptor 4
CHEMBL5017
Ki 6.58 6.58 264.0 1
D(1A) dopamine receptor
CHEMBL2056
Ki 6.06 6.06 864.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 6.0 6.0 1000.0 1
5-hydroxytryptamine receptor 4
CHEMBL5017
IC50 5.8 5.8 1584.0 1
D(1A) dopamine receptor
CHEMBL2056
IC50 5.76 5.76 1728.0 1
Beta-2 adrenergic receptor
CHEMBL210
Ki 5.72 5.72 1898.0 1
Beta-1 adrenergic receptor
CHEMBL213
Ki 5.62 5.62 2392.0 1
Beta-2 adrenergic receptor
CHEMBL210
IC50 5.56 5.56 2761.0 1
Thromboxane-A synthase
CHEMBL1835
IC50 5.51 5.51 3064.0 1
Tyrosine-protein kinase Fyn
CHEMBL1841
IC50 5.5 5.5 3160.0 1
Beta-1 adrenergic receptor
CHEMBL213
IC50 5.38 5.38 4142.0 1
Tyrosine-protein kinase Lck
CHEMBL258
IC50 5.19 5.19 6499.0 1
ATP-dependent translocase ABCB1
CHEMBL4302
Ki 4.85 4.425 14250.0 2
Gastrin/cholecystokinin type B receptor
CHEMBL2854
IC50 4.77 4.77 17000.0 1
ATP-dependent translocase ABCB1
CHEMBL3467
Ki 4.75 4.75 18000.0 1
Cholecystokinin receptor type A
CHEMBL2798
IC50 4.47 4.47 34000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 15.0 mL.min-1.kg-1 Homo sapiens
Fu 0.02 - -
Fu 0.003 - -
Fu 0.02 - Homo sapiens
Fu 0.02 - Homo sapiens
MRT 4.0 hr Homo sapiens
T1/2 2.1 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
5-hydroxytryptamine receptor 1B Ki = 0.091 nM 10.04 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1B radioligand binding (ligand: ... -
5-hydroxytryptamine receptor 1B IC50 = 0.201 nM 9.7 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1B radioligand binding (ligand: ... -
5-hydroxytryptamine receptor 1A Ki = 0.443 nM 9.35 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: ... -
5-hydroxytryptamine receptor 1A IC50 = 0.774 nM 9.11 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT1A radioligand binding (ligand: ... -
Alpha-2A adrenergic receptor Ki = 0.796 nM 9.1 DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912) -
5-hydroxytryptamine receptor 1D Ki = 0.8 nM 9.1 Compound was evaluated for its binding affinity towards human 5-hydroxytryptamin... 10715164
5-hydroxytryptamine receptor 6 Ki = 0.948 nM 9.02 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [... -
D(2) dopamine receptor Ki = 1.433 nM 8.84 DRUGMATRIX: Dopamine D2L radioligand binding (ligand: [3H] Spiperone) -
D(3) dopamine receptor Ki = 1.464 nM 8.83 DRUGMATRIX: Dopamine D3 radioligand binding (ligand: [3H] Spiperone) -
Alpha-2B adrenergic receptor Ki = 1.755 nM 8.76 DRUGMATRIX: Alpha-2B adrenergic receptor radioligand binding (ligand: Rauwolscin... -
Alpha-2C adrenergic receptor Ki = 1.809 nM 8.74 DRUGMATRIX: Adrenergic Alpha-2C radioligand binding (ligand: [3H] MK-912) -
5-hydroxytryptamine receptor 2A Ki = 1.853 nM 8.73 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2A radioligand binding (ligand: ... -
5-hydroxytryptamine receptor 6 IC50 = 2.042 nM 8.69 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT6 radioligand binding (ligand: [... -
5-hydroxytryptamine receptor 1B Ki = 2.1 nM 8.68 Displacement of [3H]carboxytryptamine from recombinant human 5-HT1B receptor exp... 21982496
Alpha-2A adrenergic receptor IC50 = 2.123 nM 8.67 DRUGMATRIX: Alpha-2A adrenergic receptor radioligand binding (ligand: MK-912) -
5-hydroxytryptamine receptor 1D Ki = 2.2 nM 8.66 Displacement of [3H]5-CT from 5-HT1D receptor (unknown origin) 24365159
5-hydroxytryptamine receptor 2B Ki = 2.203 nM 8.66 DRUGMATRIX: Serotonin (5-Hydroxytryptamine) 5-HT2B radioligand binding (ligand: ... -
Unchecked Ki = 2.43 nM 8.61 DRUGMATRIX: Imidazoline I2, Central radioligand binding (ligand: [3H] Idazoxan) -
5-hydroxytryptamine receptor 1D Ki = 2.63 nM 8.58 Displacement of [3H]5-CT from 5-HT1D receptor (unknown origin) 24365159
5-hydroxytryptamine receptor 1B Ki = 3.02 nM 8.52 Displacement of [3H]5-CT from 5-HT1B receptor (unknown origin) 24365159

Literature References

PubMed DOI Target Context # Activities
- 10.5281/zenodo.13943903 ADMET 58
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
12061889 10.1021/jm0200409 ADMET 5
18426954 10.1124/dmd.108.020479 ADMET 4
38505858 10.1021/acsmedchemlett.4c00058 5-hydroxytryptamine receptor 2A 3
20014752 10.1021/tx900326k Hepatotoxicity 3
11961113 10.1124/mol.61.5.964 ATP-dependent translocase ABCB1 2
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 2
12235267 10.1124/jpet.102.037549 ATP-dependent translocase ABCB1 2
24365159 10.1016/j.bmcl.2013.12.024 5-hydroxytryptamine receptor 5A 2
29939744 10.1021/acs.jmedchem.8b00435 5-hydroxytryptamine receptor 1B 2
24365159 10.1016/j.bmcl.2013.12.024 5-hydroxytryptamine receptor 1D 2
18834112 10.1021/jm800656v Amine oxidase [flavin-containing] B 2
37468498 10.1038/s41467-023-40064-9 Glucocorticoid receptor 2
24365159 10.1016/j.bmcl.2013.12.024 5-hydroxytryptamine receptor 1B 2
29939744 10.1021/acs.jmedchem.8b00435 5-hydroxytryptamine receptor 2B 2
14971904 10.1021/jm030408h ADMET 2
37468498 10.1038/s41467-023-40064-9 Peroxisome proliferator-activated receptor gamma 2

Data from ChEMBL 36 via Core Engine