Pomalidomide

Identification

Summary

Pomalidomide is a thalidomide analogue used in combination with dexamethasone to treat patients with multiple myeloma.

Brand Names
Imnovid, Pomalyst
Generic Name
Pomalidomide
DrugBank Accession Number
DB08910
Background

Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 273.2441
Monoisotopic: 273.074955855
Chemical Formula
C13H11N3O4
Synonyms
  • Pomalidomida
  • Pomalidomide
External IDs
  • CC-4047

Pharmacology

Indication

Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and bortezomib and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times).

Mechanism of action

Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2.

TargetActionsOrganism
AProtein cereblon
inhibitor
Humans
ATumor necrosis factor
inhibitor
Humans
AProstaglandin G/H synthase 2
inhibitor
Humans
Absorption

Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses.

Volume of distribution

Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L

Protein binding

12-44% protein bound. It is not concentration dependent.

Metabolism

Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro.

Route of elimination

When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively.

Half-life

Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours.

Clearance

Total body clearance = 7-10 L/hour

Adverse Effects
Adverseeffects
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Toxicity

Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of adverse effects can be increased when Pomalidomide is combined with 1,2-Benzodiazepine.
AbacavirAbacavir may decrease the excretion rate of Pomalidomide which could result in a higher serum level.
AbametapirThe serum concentration of Pomalidomide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Pomalidomide can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Pomalidomide.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Pomalidomide.
AbirateroneThe serum concentration of Pomalidomide can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Pomalidomide can be decreased when combined with Acalabrutinib.
AceclofenacAceclofenac may decrease the excretion rate of Pomalidomide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Pomalidomide which could result in a higher serum level.
Interactions
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Food Interactions
  • Take at the same time every day.
  • Take with or without food. Administration of pomalidomide with food reduces the AUC and Cmax by 8% and 27%, respectively, and delays Tmax by two and a half hours.

Products

Products2
Drug product information from 10+ global regions
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dosage, form, labeller, route of administration, and marketing period.
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Access drug product information from over 10 global regions.
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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ImnovidCapsule1 mgOralBristol Myers Squibb Pharma Eeig2020-12-21Not applicableEU flag
ImnovidCapsule2 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
ImnovidCapsule3 mgOralBristol Myers Squibb Pharma Eeig2020-12-21Not applicableEU flag
ImnovidCapsule4 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
ImnovidCapsule1 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
ImnovidCapsule2 mgOralBristol Myers Squibb Pharma Eeig2020-12-21Not applicableEU flag
ImnovidCapsule3 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
ImnovidCapsule4 mgOralBristol Myers Squibb Pharma Eeig2020-12-21Not applicableEU flag
PomalystCapsule3 mg/1OralCelgene Corporation2013-02-18Not applicableUS flag
PomalystCapsule4 mgOralCelgene2014-02-24Not applicableCanada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
IPOPRINPomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg)Capsule, coatedOralMsn Laboratories Private Limited2019-12-132025-01-08Colombia flag
IPOPRINPomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg)Capsule, coatedOralMsn Laboratories Private Limited2019-12-132025-01-08Colombia flag
IPOPRINPomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg)Capsule, coatedOralMsn Laboratories Private Limited2019-12-132025-01-08Colombia flag

Categories

ATC Codes
L04AX06 — Pomalidomide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phthalimides. These are aromatic heterocyclic compounds containing a 1,3-dioxoisoindoline moiety. They are imide derivatives of phthalic anhydrides.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoindoles and derivatives
Sub Class
Isoindolines
Direct Parent
Phthalimides
Alternative Parents
Alpha amino acids and derivatives / Isoindoles / Piperidinediones / Delta lactams / N-substituted carboxylic acid imides / Benzenoids / Vinylogous amides / N-unsubstituted carboxylic acid imides / Dicarboximides / Azacyclic compounds
show 5 more
Substituents
Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid imide / Carboxylic acid imide, n-substituted
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dicarboximide, aromatic amine, piperidones, isoindoles (CHEBI:72690)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
D2UX06XLB5
CAS number
19171-19-8
InChI Key
UVSMNLNDYGZFPF-UHFFFAOYSA-N
InChI
InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)
IUPAC Name
4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
SMILES
NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O

References

General References
  1. Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [Article]
  2. McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [Article]
  3. Terpos E, Kanellias N, Christoulas D, Kastritis E, Dimopoulos MA: Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. Onco Targets Ther. 2013 May 10;6:531-8. doi: 10.2147/OTT.S34498. Print 2013. [Article]
KEGG Drug
D08976
PubChem Compound
134780
PubChem Substance
175427148
ChemSpider
118785
BindingDB
65456
RxNav
1369713
ChEBI
72690
ChEMBL
CHEMBL43452
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pomalidomide
FDA label
Download (292 KB)
MSDS
Download (479 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentMultiple Myeloma (MM)1
3Active Not RecruitingTreatmentMultiple Myeloma (MM)4
3Active Not RecruitingTreatmentPlasma Cell Myeloma1
3CompletedTreatmentMPN-associated Myelofibrosis / Primary Myelofibrosis (PMF)1
3CompletedTreatmentMultiple Myeloma (MM)3
3Not Yet RecruitingTreatmentMultiple Myeloma (MM)1
3RecruitingTreatmentMultiple Myeloma (MM)6
3RecruitingTreatmentRelapsed Multiple Myeloma1
3TerminatedTreatmentMultiple Myeloma (MM)2
3Unknown StatusTreatmentMultiple Myeloma (MM)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Capsule, coatedOral
CapsuleOral1 mg/1
CapsuleOral2 mg/1
CapsuleOral3 mg/1
CapsuleOral4 mg/1
Capsule, coatedOral1 mg
CapsuleOral1 mg
CapsuleOral2 mg
CapsuleOral3 mg
CapsuleOral4 mg
CapsuleOral
Capsule, coatedOral2 mg
Capsule, coatedOral3 mg
Capsule, coatedOral4 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6045501No2000-04-042018-08-28US flag
US6315720No2001-11-132020-10-23US flag
US6561976No2003-05-132018-08-28US flag
US6561977No2003-05-132020-10-23US flag
US6755784No2004-06-292020-10-23US flag
US6908432No2005-06-212018-08-28US flag
US8204763No2012-06-192018-08-28US flag
US8315886No2012-11-202020-10-23US flag
US8626531No2014-01-072020-10-23US flag
US8589188No2013-11-192018-08-28US flag
US5635517No1997-06-032019-10-04US flag
US6316471No2001-11-132016-08-10US flag
US6476052No2002-11-052016-07-24US flag
US8198262Yes2012-06-122025-12-17US flag
US8673939Yes2014-03-182023-11-15US flag
US8735428Yes2014-05-272023-11-15US flag
US8828427Yes2014-09-092031-12-21US flag
US8158653No2012-04-172016-08-10US flag
US9993467Yes2018-06-122030-11-19US flag
US10555939Yes2020-02-112030-11-19US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.57 mg/mLALOGPS
logP0.02ALOGPS
logP-0.16ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)11.59ChemAxon
pKa (Strongest Basic)1.56ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area109.57 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity69.03 m3·mol-1ChemAxon
Polarizability25.81 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9653
Blood Brain Barrier+0.8304
Caco-2 permeable-0.6419
P-glycoprotein substrateSubstrate0.5264
P-glycoprotein inhibitor INon-inhibitor0.5983
P-glycoprotein inhibitor IINon-inhibitor0.9147
Renal organic cation transporterNon-inhibitor0.847
CYP450 2C9 substrateNon-substrate0.844
CYP450 2D6 substrateNon-substrate0.8882
CYP450 3A4 substrateSubstrate0.5079
CYP450 1A2 substrateNon-inhibitor0.8863
CYP450 2C9 inhibitorNon-inhibitor0.8428
CYP450 2D6 inhibitorNon-inhibitor0.9002
CYP450 2C19 inhibitorNon-inhibitor0.8513
CYP450 3A4 inhibitorNon-inhibitor0.7289
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8686
Ames testNon AMES toxic0.7979
CarcinogenicityNon-carcinogens0.9081
BiodegradationNot ready biodegradable0.9858
Rat acute toxicity2.5862 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9885
hERG inhibition (predictor II)Non-inhibitor0.7765
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-1590000000-a511655f5e07f3ab2179

Targets

Drugtargets2
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insights and accelerate drug research.
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Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Norma...
Gene Name
CRBN
Uniprot ID
Q96SW2
Uniprot Name
Protein cereblon
Molecular Weight
50545.375 Da
References
  1. McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [Article]
  2. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H: Identification of a primary target of thalidomide teratogenicity. Science. 2010 Mar 12;327(5971):1345-50. doi: 10.1126/science.1177319. [Article]
  3. Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R: Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
References
  1. Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Ferguson GD, Jensen-Pergakes K, Wilkey C, Jhaveri U, Richard N, Verhelle D, De Parseval LM, Corral LG, Xie W, Morris CL, Brady H, Chan K: Immunomodulatory drug CC-4047 is a cell-type and stimulus-selective transcriptional inhibitor of cyclooxygenase 2. J Clin Immunol. 2007 Mar;27(2):210-20. Epub 2007 Feb 17. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Li Y, Xu Y, Liu L, Wang X, Palmisano M, Zhou S: Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72. doi: 10.1002/jcph.455. Epub 2015 Feb 4. [Article]
  2. Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]
  3. Pomalidomide FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]

Drug created on June 20, 2013 22:45 / Updated on October 22, 2021 23:18