Target Information

Target General Infomation
Target ID
T38950
Former ID
TTDS00091
Target Name
Myeloid cell surface antigen CD33
Gene Name
CD33
Synonyms
Gp67; Siglec-3; CD33
Target Type
Successful
Disease Acute myeloid leukemia [ICD9: 205; ICD10: C92.0]
Leukemia [ICD9: 208.9; ICD10: C90-C95]
Function
Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,6-linked sialic acid. The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Induces apoptosis in acute myeloid leukemia (in vitro).
BioChemical Class
Immunoglobulin
UniProt ID
P20138
Sequence
MPLLLLLPLLWAGALAMDPNFWLQVQESVTVQEGLCVLVPCTFFHPIPYYDKNSPVHGYW
FREGAIISRDSPVATNKLDQEVQEETQGRFRLLGDPSRNNCSLSIVDARRRDNGSYFFRM
ERGSTKYSYKSPQLSVHVTDLTHRPKILIPGTLEPGHSKNLTCSVSWACEQGTPPIFSWL
SAAPTSLGPRTTHSSVLIITPRPQDHGTNLTCQVKFAGAGVTTERTIQLNVTYVPQNPTT
GIFPGDGSGKQETRAGVVHGAIGGAGVTALLALCLCLIFFIVKTHRRKAARTAVGRNDTH
PTTGSASPKHQKKSKLHGPTETSSCSGAAPTVEMDEELHYASLNFHGMNPSKDTSTEYSE
VRTQ
Drugs and Mode of Action
Drug(s) Gemtuzumab ozogamicin Drug Info Approved Acute myeloid leukemia [536361], [541855]
HuM-195-Ac-225 Drug Info Phase 1/2 Acute myeloid leukemia [550199]
BI-836858 Drug Info Phase 1 Acute myeloid leukemia [524065]
HuM195/rGel Drug Info Phase 1 Leukemia [546349]
SGN-CD33A Drug Info Phase 1 Acute myeloid leukemia [549492]
Lintuzumab Drug Info Discontinued in Phase 2 Leukemia [542898], [547399]
HuM-195-Bi-213 Drug Info Discontinued in Phase 1/2 Acute myeloid leukemia [546496]
Oncolysin M Drug Info Discontinued in Phase 1 Leukemia [545607]
Inhibitor HuM-195-Ac-225 Drug Info [549712]
HuM-195-Bi-213 Drug Info [531172]
Modulator Oncolysin M Drug Info [550922]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway Hematopoietic cell lineage
Reactome Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
References
Ref 524065ClinicalTrials.gov (NCT01690624) BI 836858 Dose Escalation in Refractory or Relapsed Acute Myeloid Leukemia. U.S. National Institutes of Health.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 541855(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6775).
Ref 542898(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7983).
Ref 545607Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003885)
Ref 546349Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007636)
Ref 546496Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008571)
Ref 547399Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800015937)
Ref 549492Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800038378)
Ref 550199Clinical pipeline report, company report or official report of Actinium Pharmaceuticals.
Ref 527596Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia. J Clin Oncol. 2005 Jun 20;23(18):4110-6.
Ref 531172Sequential cytarabine and alpha-particle immunotherapy with bismuth-213-lintuzumab (HuM195) for acute myeloid leukemia. Clin Cancer Res. 2010 Nov 1;16(21):5303-11.
Ref 531997Phase 1 study of an anti-CD33 immunotoxin, humanized monoclonal antibody M195 conjugated to recombinant gelonin (HUM-195/rGEL), in patients with advanced myeloid malignancies. Haematologica. 2013 Feb;98(2):217-21.
Ref 532400SGN-CD33A: a novel CD33-targeting antibody-drug conjugate using a pyrrolobenzodiazepine dimer is active in models of drug-resistant AML. Blood. 2013 Aug 22;122(8):1455-63.
Ref 532771The past and future of CD33 as therapeutic target in acute myeloid leukemia. Blood Rev. 2014 Jul;28(4):143-53.
Ref 535660Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov. 2003 Jan;2(1):38-51.
Ref 537216Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study. Int J Hematol. 2009 May;89(4):460-9. Epub 2009 Apr 10.
Ref 537245Successful treatment with gemtuzumab ozogamicin monotherapy in a pediatric patient with resistant relapse of acute myeloid leukemia. Turk J Pediatr. 2009 Jan-Feb;51(1):69-71.
Ref 537367Deficient activation of Bak and Bax confers resistance to gemtuzumab ozogamicin-induced apoptotic cell death in AML. Exp Hematol. 2009 Jun;37(6):755-66.
Ref 537432Targeted treatment of acute myeloid leukemia in older adults: role of gemtuzumab ozogamicin. Clin Interv Aging. 2009;4(1):197-205. Epub 2009 May 14.
Ref 549712J Clin Oncol 29: 2011 (suppl; abstr 6516).
Ref 550922US patent application no. 6,926,898, Albumin fusion proteins.

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