Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTJ2PTI)

• DTT Name: Tubulin beta-2 chain (TUBB2)
• Synonyms: Tubulin beta-2A chain; Tubulin beta class IIa; TUBB4B; BetaII-Tubulin; Beta(II)-Tubulin; Beta(II) isotype of Tubulin
• Gene Name: TUBB2A
• DTT Type: Successful target; [1]
• UniProt ID: TBB2A_HUMAN
• TTD ID: T28661
• Sequence:
  MREIVHIQAGQCGNQIGAKFWEVISDEHGIDPTGSYHGDSDLQLERINVYYNEAAGNKYV
  PRAILVDLEPGTMDSVRSGPFGQIFRPDNFVFGQSGAGNNWAKGHYTEGAELVDSVLDVV
  RKESESCDCLQGFQLTHSLGGGTGSGMGTLLISKIREEYPDRIMNTFSVMPSPKVSDTVV
  EPYNATLSVHQLVENTDETYSIDNEALYDICFRTLKLTTPTYGDLNHLVSATMSGVTTCL
  RFPGQLNADLRKLAVNMVPFPRLHFFMPGFAPLTSRGSQQYRALTVPELTQQMFDSKNMM
  AACDPRHGRYLTVAAIFRGRMSMKEVDEQMLNVQNKNSSYFVEWIPNNVKTAVCDIPPRG
  LKMSATFIGNSTAIQELFKRISEQFTAMFRRKAFLHWYTGEGMDEMEFTEAESNMNDLVS
  EYQQYQDATADEQGEFEEEEGEDEA
• Function: It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. Tubulin is the major constituent of microtubules.
• KEGG Pathway:
  Phagosome (hsa04145)
  Gap junction (hsa04540)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Salmonella infection (hsa05132)
• Reactome Pathway:
  Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane (R-HSA-190840)
  Gap junction assembly (R-HSA-190861)
  MHC class II antigen presentation (R-HSA-2132295)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand (R-HSA-3371497)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Prefoldin mediated transfer of substrate to CCT/TriC (R-HSA-389957)
  Formation of tubulin folding intermediates by CCT/TriC (R-HSA-389960)
  Post-chaperonin tubulin folding pathway (R-HSA-389977)
  Recycling pathway of L1 (R-HSA-437239)
  Hedgehog 'off' state (R-HSA-5610787)
  Cilium Assembly (R-HSA-5617833)
  Intraflagellar transport (R-HSA-5620924)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  RHO GTPases Activate Formins (R-HSA-5663220)
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  COPI-independent Golgi-to-ER retrograde traffic (R-HSA-6811436)
  Mitotic Prometaphase (R-HSA-68877)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  Carboxyterminal post-translational modifications of tubulin (R-HSA-8955332)
  HCMV Early Events (R-HSA-9609690)
  Assembly and cell surface presentation of NMDA receptors (R-HSA-9609736)
  Activation of AMPK downstream of NMDARs (R-HSA-9619483)
  Aggrephagy (R-HSA-9646399)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Sealing of the nuclear envelope (NE) by ESCRT-III (R-HSA-9668328)
  Kinesins (R-HSA-983189)
  Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vinblastine	DM5TVS3	Advanced cancer	2A00-2F9Z	Approved	[1]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DOLASTATIN-10	DMDUV1S	Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]

11 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2'-amino-3,4,4',5-tetramethoxy-(Z)-stillbene	DMUYZA8	Discovery agent	N.A.	Investigative	[3]
2,3'-diamino-3,4,4',5-tetramethoxy-(Z)-stillbene	DM2UWDR	Discovery agent	N.A.	Investigative	[3]
2-amino-3,4',5-trimethoxy-(Z)-stillbene	DMMZ2LI	Discovery agent	N.A.	Investigative	[3]
3,4',5-trimethoxy-(Z)-stilbene	DMYHC3S	Discovery agent	N.A.	Investigative	[3]
3,4,4',5-tetramethoxy-(Z)-stilbene	DMSN814	Discovery agent	N.A.	Investigative	[3]
3-bromo-4,4',5-trimethoxy-(Z)-stilbene	DMPZ4M8	Discovery agent	N.A.	Investigative	[3]
6-ile-ustiloxin	DMQF8JG	Discovery agent	N.A.	Investigative	[2]
N-(4-(3-(pyridin-2-yl)acryloyl)phenyl)acetamide	DMRH987	Discovery agent	N.A.	Investigative	[4]
USTILOXIN A	DMZP32O	Discovery agent	N.A.	Investigative	[2]
Ustiloxin D	DMA8JH7	Discovery agent	N.A.	Investigative	[2]
Ustiloxin F	DMT1LS0	Discovery agent	N.A.	Investigative	[2]

References

• [1] Effect of the antitumor drug vinblastine on nuclear betaII-tubulin in cultured rat kidney mesangial cells. Invest New Drugs. 2003 Feb;21(1):15-20.
• [2] Total synthesis and biological evaluation of ustiloxin natural products and two analogs. Bioorg Med Chem Lett. 2006 Sep 15;16(18):4804-7.
• [3] 2-amino and 2'-aminocombretastatin derivatives as potent antimitotic agents. J Med Chem. 2006 Oct 19;49(21):6412-5.
• [4] Design and biological evaluation of novel tubulin inhibitors as antimitotic agents using a pharmacophore binding model with tubulin. J Med Chem. 2006 Sep 21;49(19):5664-70.