Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQO71U)

• DTT Name: Hemoglobin (HB)
• Synonyms: Hemoglobin subunit alpha; Hemoglobin alpha chain; HBA1; Alpha-globin
• Gene Name: HBA2
• DTT Type: Successful target; [1]
• BioChemical Class: Pore-forming globin
• UniProt ID: HBA_HUMAN
• TTD ID: T49493
• Sequence:
  MVLSPADKTNVKAAWGKVGAHAGEYGAEALERMFLSFPTTKTYFPHFDLSHGSAQVKGHG
  KKVADALTNAVAHVDDMPNALSALSDLHAHKLRVDPVNFKLLSHCLLVTLAAHLPAEFTP
  AVHASLDKFLASVSTVLTSKYR
• Function: Involved in oxygen transport from the lung to the various peripheral tissues.
• KEGG Pathway:
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
• Reactome Pathway:
  Erythrocytes take up oxygen and release carbon dioxide (R-HSA-1247673)
  Scavenging of heme from plasma (R-HSA-2168880)
  Erythrocytes take up carbon dioxide and release oxygen (R-HSA-1237044)

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Iron	DMAP8MV	Anemia of prematurity		Approved	[1]
Iron Dextran	DM5OY70	Iron-deficiency anemia	3A00	Approved	[1]
Voxelotor	DMCS6M5	Sickle-cell disorder	3A51	Approved	[2]

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Efaproxyn	DMX7BM4	Lung cancer	2C25.0	Phase 3	[3]
PolyHeme	DMV8EXG	Blood forming organ disorder	JB64.1	Phase 3	[4]
GBT021601	DMD3C21	Sickle-cell disorder	3A51	Phase 2/3	[5]
Hemoglobin raffimer	DMMTL7V	Anemia	3A00-3A9Z	Phase 2/3	[6]
5-hydroxymethyl-2-furfural	DMPFVJB	Anemia	3A00-3A9Z	Phase 2	[7]
FBS-0701	DMR3952	Iron overload disease	5C64.10	Phase 2	[8]
HQK-1001	DM7QUN0	Beta thalassemia	3A50.2	Phase 2	[9]
CTX110	DMJ7LP0	Non-hodgkin lymphoma	2B33.5	Phase 1/2	[10]
OXY-111A	DMTH75R	Cardiovascular disease	BA00-BE2Z	Phase 1/2	[11]

9 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hemoximer	DMGYKDN	Hypotension	BA20-BA21	Discontinued in Phase 3	[12]
VX-366	DMH4U87	Constitutional neutropenia	4B00.0	Discontinued in Phase 2	[13]
HRC-302	DMH32LM	Chronic myelogenous leukaemia	2A20.0	Discontinued in Phase 1	[14]
AN-10	DM50HB8	Alopecia	ED70	Terminated	[15]
Diaspirin crosslinked hemoglobin	DM61BWZ	Cerebrovascular ischaemia	8B1Z	Terminated	[16]
HRC-101	DMEZ5P2	Blood transfusion	QB98	Terminated	[17]
HRC-102	DMJACXN	Reperfusion injury	ND56.Z	Terminated	[18]
HRC-201	DM5A3GX	Liver cancer	2C12	Terminated	[18]
RHb1.1	DM7CY0T	Anemia	3A00-3A9Z	Terminated	[19]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,3,5-BENZENETRICARBOXYLIC ACID	DMNCWXZ	Discovery agent	N.A.	Investigative	[20]
2,6-DICARBOXYNAPHTHALENE	DM8JFNU	Discovery agent	N.A.	Investigative	[20]
2-[(2-methoxy-5-methylphenoxy)methyl]pyridine	DMXA1LK	Discovery agent	N.A.	Investigative	[20]
4-Carboxycinnamic Acid	DMBIQV3	Discovery agent	N.A.	Investigative	[20]
4-[(5-methoxy-2-methylphenoxy)methyl]pyridine	DMNMC9O	Discovery agent	N.A.	Investigative	[20]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[20]
SEBACIC ACID	DM3VOPQ	Discovery agent	N.A.	Investigative	[20]

References

• [1] Efficacy and safety of total dose infusion of low molecular weight iron dextran in the treatment of iron deficiency anemia during pregnancy. J Coll Physicians Surg Pak. 2008 Jul;18(7):424-7.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [3] Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1503-9.
• [4] Blood substitutes- the polyheme trials. Mcgill J Med. 2008 January; 11(1): 59-65.
• [5] GBT021601 improves red blood cell health and the pathophysiology of sickle cell disease in a murine model. Br J Haematol. 2023 Jul;202(1):173-183.
• [6] Use of hemoglobin raffimer for postoperative life-threatening anemia in a Jehovah's Witness. Can J Anaesth. 2005 Apr;52(4):369-73.
• [7] 5-hydroxymethyl-2-furfural modifies intracellular sickle haemoglobin and inhibits sickling of red blood cells. Br J Haematol. 2005 Feb;128(4):552-61.
• [8] A high-affinity fully human anti-IL-6 mAb, 1339, for the treatment of multiple myeloma. Clin Cancer Res. 2009 Dec 1;15(23):7144-52.
• [9] A phase 2 study of HQK-1001, an oral fetal haemoglobin inducer, in beta-thalassaemia intermedia. Br J Haematol. 2014 Feb;164(3):456-8.
• [10] Clinical pipeline report, company report or official report of CRISPR Therapeutics.
• [11] Modulating the oxygen affinity of human fetal haemoglobin with synthetic allosteric modulators. Br J Haematol. 1998 Sep;102(5):1165-71.
• [12] Effect of NaBH4 Concentration and Reaction Time on Physical Properties of Glutaraldehyde-Polymerized Hemoglobin. Biotechnology Progress. 05/2004; 20(3):946-52.
• [13] A combination of hydroxyurea and isobutyramide to induce fetal hemoglobin in transgenic mice is more hematotoxic than the individual agents. Blood Cells Mol Dis. 1999 Jun-Aug;25(3-4):255-69.
• [14] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014790)
• [15] Genes for Development, Cell Growth and Infectious Diseases, Gabriel Gachelin, 1995. Page(215).
• [16] Diaspirin cross-linked hemoglobin infusion did not influence base deficit and lactic acid levels in two clinical trials of traumatic hemorrhagic shock patient resuscitation. J Trauma. 2010 May;68(5):1158-71.
• [17] The novel hemoglobin-based oxygen carrier HRC 101 improves survival in murine sickle cell disease. Anesthesiology. 2007 Aug;107(2):281-7.
• [18] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [19] Effects of recombinant-hemoglobin solutions rHb2.0 and rHb1.1 on blood pressure, intestinal blood flow, and gut oxygenation in a rat model of hemorrhagic shock. J Lab Clin Med. 2005 Jan;145(1):21-32.
• [20] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.