Pentamidine (T3D3526)

General Function:

Used for biological information storage.

Specific Function:

DNA contains the instructions needed for an organism to develop, survive and reproduce.

Molecular Weight:

2.15 x 10¹² Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
3. Shankar SM, Nania JJ: Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy. Paediatr Drugs. 2007;9(5):301-9. [17927302 ]

General Function:

Zinc ion binding

Specific Function:

Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.

Gene Name:

S100B

Uniprot ID:

P04271

Molecular Weight:

10712.985 Da

References

1. Markowitz J, Chen I, Gitti R, Baldisseri DM, Pan Y, Udan R, Carrier F, MacKerell AD Jr, Weber DJ: Identification and characterization of small molecule inhibitors of the calcium-dependent S100B-p53 tumor suppressor interaction. J Med Chem. 2004 Oct 7;47(21):5085-93. [15456252 ]
2. Yoshimura C, Miyafusa T, Tsumoto K: Identification of small-molecule inhibitors of the human S100B-p53 interaction and evaluation of their activity in human melanoma cells. Bioorg Med Chem. 2013 Mar 1;21(5):1109-15. doi: 10.1016/j.bmc.2012.12.042. Epub 2013 Jan 8. [23375094 ]

General Function:

Peptidyl-cysteine s-nitrosylase activity

Specific Function:

Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation.

Gene Name:

GAPDH

Uniprot ID:

P04406

Molecular Weight:

36053.0 Da

References

1. Bressi JC, Verlinde CL, Aronov AM, Shaw ML, Shin SS, Nguyen LN, Suresh S, Buckner FS, Van Voorhis WC, Kuntz ID, Hol WG, Gelb MH: Adenosine analogues as selective inhibitors of glyceraldehyde-3-phosphate dehydrogenase of Trypanosomatidae via structure-based drug design. J Med Chem. 2001 Jun 21;44(13):2080-93. [11405646 ]

General Function:

Monovalent cation:proton antiporter activity

Specific Function:

Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.

Gene Name:

SLC47A1

Uniprot ID:

Q96FL8

Molecular Weight:

61921.585 Da

References

1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

General Function:

Drug transmembrane transporter activity

Specific Function:

Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, and ganciclovir. Responsible for the secretion of cationic drugs across the brush border membranes.

Gene Name:

SLC47A2

Uniprot ID:

Q86VL8

Molecular Weight:

65083.915 Da

References

1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

General Function:

Secondary active organic cation transmembrane transporter activity

Specific Function:

Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.

Gene Name:

SLC22A1

Uniprot ID:

O15245

Molecular Weight:

61153.345 Da

References

1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

General Function:

Quaternary ammonium group transmembrane transporter activity

Specific Function:

Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.

Gene Name:

SLC22A2

Uniprot ID:

O15244

Molecular Weight:

62579.99 Da

References

1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

General Function:

Toxin transporter activity

Specific Function:

Mediates potential-dependent transport of a variety of organic cations. May play a significant role in the disposition of cationic neurotoxins and neurotransmitters in the brain.

Gene Name:

SLC22A3

Uniprot ID:

O75751

Molecular Weight:

61279.485 Da

References

1. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]

General Function:

Serine-type peptidase activity

Specific Function:

Degrades extracellular matrix. Proposed to play a role in breast cancer invasion and metastasis. Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site. Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing.

Gene Name:

ST14

Uniprot ID:

Q9Y5Y6

Molecular Weight:

94769.01 Da

References

1. Enyedy IJ, Lee SL, Kuo AH, Dickson RB, Lin CY, Wang S: Structure-based approach for the discovery of bis-benzamidines as novel inhibitors of matriptase. J Med Chem. 2001 Apr 26;44(9):1349-55. [11311057 ]

General Function:

Trna methyltransferase activity

Specific Function:

Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).

Gene Name:

TRDMT1

Uniprot ID:

O14717

Molecular Weight:

44596.17 Da

References

1. Sun T, Zhang Y: Pentamidine binds to tRNA through non-specific hydrophobic interactions and inhibits aminoacylation and translation. Nucleic Acids Res. 2008 Mar;36(5):1654-64. doi: 10.1093/nar/gkm1180. Epub 2008 Feb 7. [18263620 ]

General Function:

Protein tyrosine/serine/threonine phosphatase activity

Specific Function:

Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.

Gene Name:

PTP4A3

Uniprot ID:

O75365

Molecular Weight:

19534.69 Da