Details of the Target

General Information of Target

Target ID LDTP01769
Target Name Dihydrofolate reductase (DHFR)
Gene Name DHFR
Gene ID 1719
Synonyms
Dihydrofolate reductase; EC 1.5.1.3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFS
IPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSS
VYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKF
EVYEKND
Target Type
Successful
Target Bioclass
Enzyme
Family
Dihydrofolate reductase family
Subcellular location
Mitochondrion
Function
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFR2.
TTD ID
T17345
Uniprot ID
P00374
DrugMap ID
TTYZVDJ
Ensemble ID
ENST00000439211.7
HGNC ID
HGNC:2861
ChEMBL ID
CHEMBL202

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
RKO SNV: p.T57A .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 25 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FBPP2
 Probe Info  		6.68  LDD0318  [1]
TH211
 Probe Info  		Y157(13.12); Y163(5.47)  LDD0257  [2]
TH216
 Probe Info  		Y122(17.99); Y157(16.91); Y163(6.94)  LDD0259  [2]
STPyne
 Probe Info  		K174(8.06)  LDD0277  [3]
P11
 Probe Info  		20.00  LDD0201  [4]
DBIA
 Probe Info  		C7(1.42)  LDD2836  [5]
MCL-14
 Probe Info  		3.00  LDD0050  [6]
HHS-475
 Probe Info  		Y163(0.82)  LDD0264  [7]
HHS-465
 Probe Info  		Y163(5.12)  LDD2237  [8]
5E-2FA
 Probe Info  		N.A.  LDD2235  [9]
ATP probe
 Probe Info  		K174(0.00); K177(0.00)  LDD0199  [10]
m-APA
 Probe Info  		H128(0.00); H88(0.00)  LDD2231  [9]
4-Iodoacetamidophenylacetylene
 Probe Info  		N.A.  LDD0038  [11]
IA-alkyne
 Probe Info  		N.A.  LDD0036  [11]
Lodoacetamide azide
 Probe Info  		N.A.  LDD0037  [11]
ATP probe
 Probe Info  		N.A.  LDD0035  [12]
IPM
 Probe Info  		N.A.  LDD0025  [13]
JW-RF-010
 Probe Info  		N.A.  LDD0026  [13]
TFBX
 Probe Info  		N.A.  LDD0027  [13]
NHS
 Probe Info  		N.A.  LDD0010  [14]
SF
 Probe Info  		Y178(0.00); Y163(0.00)  LDD0028  [15]
1c-yne
 Probe Info  		K81(0.00); K109(0.00)  LDD0228  [16]
AOyne
 Probe Info  		11.60  LDD0443  [17]
NAIA_5
 Probe Info  		N.A.  LDD2223  [18]
TER-AC
 Probe Info  		N.A.  LDD0426  [19]
PAL-AfBPP Probe
Click To Hide/Show 111 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C004
 Probe Info  		9.92  LDD1714  [20]
C007
 Probe Info  		7.06  LDD1716  [20]
C010
 Probe Info  		6.36  LDD1719  [20]
C011
 Probe Info  		13.83  LDD1720  [20]
C018
 Probe Info  		5.50  LDD1726  [20]
C022
 Probe Info  		17.15  LDD1728  [20]
C028
 Probe Info  		7.36  LDD1734  [20]
C041
 Probe Info  		35.02  LDD1741  [20]
C044
 Probe Info  		5.46  LDD1743  [20]
C055
 Probe Info  		99.73  LDD1752  [20]
C056
 Probe Info  		16.56  LDD1753  [20]
C058
 Probe Info  		9.58  LDD1755  [20]
C059
 Probe Info  		74.03  LDD1756  [20]
C060
 Probe Info  		6.59  LDD1757  [20]
C062
 Probe Info  		9.19  LDD1759  [20]
C064
 Probe Info  		6.41  LDD1761  [20]
C085
 Probe Info  		9.32  LDD1777  [20]
C089
 Probe Info  		6.50  LDD1781  [20]
C106
 Probe Info  		64.45  LDD1793  [20]
C107
 Probe Info  		5.94  LDD1794  [20]
C108
 Probe Info  		45.25  LDD1795  [20]
C110
 Probe Info  		6.92  LDD1797  [20]
C112
 Probe Info  		17.75  LDD1799  [20]
C129
 Probe Info  		16.34  LDD1811  [20]
C130
 Probe Info  		15.24  LDD1812  [20]
C137
 Probe Info  		5.46  LDD1819  [20]
C139
 Probe Info  		54.19  LDD1821  [20]
C140
 Probe Info  		8.40  LDD1822  [20]
C141
 Probe Info  		22.47  LDD1823  [20]
C145
 Probe Info  		8.57  LDD1827  [20]
C147
 Probe Info  		30.91  LDD1829  [20]
C153
 Probe Info  		21.86  LDD1834  [20]
C159
 Probe Info  		24.25  LDD1839  [20]
C160
 Probe Info  		22.78  LDD1840  [20]
C161
 Probe Info  		21.11  LDD1841  [20]
C163
 Probe Info  		9.45  LDD1843  [20]
C168
 Probe Info  		9.19  LDD1848  [20]
C169
 Probe Info  		23.26  LDD1849  [20]
C173
 Probe Info  		5.24  LDD1853  [20]
C178
 Probe Info  		99.73  LDD1857  [20]
C183
 Probe Info  		20.25  LDD1861  [20]
C191
 Probe Info  		14.32  LDD1868  [20]
C193
 Probe Info  		8.17  LDD1869  [20]
C194
 Probe Info  		30.91  LDD1870  [20]
C195
 Probe Info  		11.08  LDD1871  [20]
C196
 Probe Info  		21.56  LDD1872  [20]
C206
 Probe Info  		44.02  LDD1881  [20]
C213
 Probe Info  		16.00  LDD1887  [20]
C218
 Probe Info  		54.95  LDD1892  [20]
C220
 Probe Info  		13.18  LDD1894  [20]
C222
 Probe Info  		18.51  LDD1896  [20]
C226
 Probe Info  		6.77  LDD1899  [20]
C228
 Probe Info  		27.86  LDD1901  [20]
C232
 Probe Info  		49.18  LDD1905  [20]
C234
 Probe Info  		8.22  LDD1907  [20]
C238
 Probe Info  		16.22  LDD1911  [20]
C240
 Probe Info  		12.47  LDD1913  [20]
C243
 Probe Info  		13.45  LDD1916  [20]
C252
 Probe Info  		12.30  LDD1925  [20]
C255
 Probe Info  		32.22  LDD1928  [20]
C257
 Probe Info  		7.36  LDD1930  [20]
C260
 Probe Info  		7.16  LDD1932  [20]
C277
 Probe Info  		36.00  LDD1947  [20]
C280
 Probe Info  		39.67  LDD1950  [20]
C282
 Probe Info  		34.30  LDD1952  [20]
C284
 Probe Info  		94.35  LDD1954  [20]
C286
 Probe Info  		4.96  LDD1956  [20]
C288
 Probe Info  		8.22  LDD1958  [20]
C290
 Probe Info  		6.11  LDD1960  [20]
C293
 Probe Info  		21.86  LDD1963  [20]
C297
 Probe Info  		16.34  LDD1967  [20]
C299
 Probe Info  		5.94  LDD1968  [20]
C301
 Probe Info  		6.68  LDD1970  [20]
C303
 Probe Info  		6.06  LDD1972  [20]
C307
 Probe Info  		6.11  LDD1975  [20]
C311
 Probe Info  		6.15  LDD1978  [20]
C326
 Probe Info  		9.13  LDD1990  [20]
C333
 Probe Info  		6.36  LDD1996  [20]
C342
 Probe Info  		7.01  LDD2004  [20]
C344
 Probe Info  		7.67  LDD2006  [20]
C347
 Probe Info  		11.31  LDD2008  [20]
C351
 Probe Info  		25.28  LDD2012  [20]
C353
 Probe Info  		23.26  LDD2014  [20]
C354
 Probe Info  		13.93  LDD2015  [20]
C361
 Probe Info  		30.70  LDD2022  [20]
C364
 Probe Info  		15.24  LDD2025  [20]
C366
 Probe Info  		6.54  LDD2027  [20]
C368
 Probe Info  		6.36  LDD2029  [20]
C370
 Probe Info  		6.59  LDD2031  [20]
C374
 Probe Info  		12.91  LDD2034  [20]
C376
 Probe Info  		18.64  LDD2036  [20]
C380
 Probe Info  		7.78  LDD2039  [20]
C382
 Probe Info  		11.08  LDD2041  [20]
C383
 Probe Info  		11.79  LDD2042  [20]
C386
 Probe Info  		23.10  LDD2045  [20]
C387
 Probe Info  		21.11  LDD2046  [20]
C388
 Probe Info  		99.73  LDD2047  [20]
C389
 Probe Info  		5.35  LDD2048  [20]
C390
 Probe Info  		24.42  LDD2049  [20]
C392
 Probe Info  		26.54  LDD2051  [20]
C395
 Probe Info  		16.80  LDD2054  [20]
C396
 Probe Info  		5.78  LDD2055  [20]
C399
 Probe Info  		10.63  LDD2058  [20]
C405
 Probe Info  		8.28  LDD2063  [20]
C429
 Probe Info  		29.24  LDD2084  [20]
C431
 Probe Info  		52.71  LDD2086  [20]
FFF probe13
 Probe Info  		20.00  LDD0475  [21]
FFF probe14
 Probe Info  		20.00  LDD0477  [21]
FFF probe15
 Probe Info  		20.00  LDD0478  [21]
FFF probe7
 Probe Info  		20.00  LDD0483  [21]
OEA-DA
 Probe Info  		20.00  LDD0046  [22]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0088  C45 HEK-293T 20.00  LDD0201  [4]
 LDCM0632  CL-Sc Hep-G2 C7(0.94)  LDD2227  [18]
 LDCM0625  F8 Ramos C7(0.47)  LDD2187  [23]
 LDCM0572  Fragment10 Ramos C7(0.46)  LDD2189  [23]
 LDCM0573  Fragment11 Ramos C7(0.07)  LDD2190  [23]
 LDCM0574  Fragment12 Ramos C7(0.78)  LDD2191  [23]
 LDCM0575  Fragment13 Ramos C7(0.68)  LDD2192  [23]
 LDCM0576  Fragment14 Ramos C7(0.84)  LDD2193  [23]
 LDCM0579  Fragment20 Ramos C7(0.53)  LDD2194  [23]
 LDCM0580  Fragment21 Ramos C7(0.72)  LDD2195  [23]
 LDCM0582  Fragment23 Ramos C7(0.60)  LDD2196  [23]
 LDCM0578  Fragment27 Ramos C7(0.62)  LDD2197  [23]
 LDCM0586  Fragment28 Ramos C7(1.01)  LDD2198  [23]
 LDCM0588  Fragment30 Ramos C7(0.48)  LDD2199  [23]
 LDCM0589  Fragment31 Ramos C7(0.86)  LDD2200  [23]
 LDCM0590  Fragment32 Ramos C7(0.56)  LDD2201  [23]
 LDCM0468  Fragment33 Ramos C7(0.54)  LDD2202  [23]
 LDCM0596  Fragment38 Ramos C7(0.86)  LDD2203  [23]
 LDCM0566  Fragment4 Ramos C7(0.64)  LDD2184  [23]
 LDCM0610  Fragment52 Ramos C7(0.50)  LDD2204  [23]
 LDCM0614  Fragment56 Ramos C7(0.43)  LDD2205  [23]
 LDCM0569  Fragment7 Ramos C7(0.48)  LDD2186  [23]
 LDCM0571  Fragment9 Ramos C7(0.61)  LDD2188  [23]
 LDCM0116  HHS-0101 DM93 Y163(0.82)  LDD0264  [7]
 LDCM0117  HHS-0201 DM93 Y163(0.69)  LDD0265  [7]
 LDCM0118  HHS-0301 DM93 Y163(0.72)  LDD0266  [7]
 LDCM0119  HHS-0401 DM93 Y163(0.80)  LDD0267  [7]
 LDCM0120  HHS-0701 DM93 Y163(0.92)  LDD0268  [7]
 LDCM0022  KB02 Ramos C7(0.41)  LDD2182  [23]
 LDCM0023  KB03 Ramos C7(0.69)  LDD2183  [23]
 LDCM0024  KB05 Ramos C7(0.38)  LDD2185  [23]
 LDCM0006  Micheliolide M9-ENL1 3.00  LDD0050  [6]
 LDCM0628  OTUB2-COV-1 HEK-293T C7(0.27)  LDD2207  [24]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 14 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Aminosalicylic Acid Small molecular drug D01WJL
Folic Acid Small molecular drug DB00158
Gentamicin Small molecular drug DB00798
Lamotrigine Small molecular drug DB00555
Leucovorin Calcium Small molecular drug D0B6TW
Methotrexate Small molecular drug DB00563
Methotrexate Sodium Small molecular drug D0D3DU
Nadh Small molecular drug DB00157
Pemetrexed Small molecular drug DB00642
Pralatrexate Small molecular drug DB06813
Proguanil Small molecular drug DB01131
Pyrimethamine Small molecular drug DB00205
Trimethoprim Small molecular drug D0AO5H
Trimetrexate Small molecular drug DB01157
Phase 3
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Iclaprim Small molecular drug D04LBC
Phase 2
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Piritrexim Small molecular drug D09AYQ
Ch-4051 . D02OTK
Phase 1
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
L-mdam Small molecular drug D0S9OH
Vyr 006 Small molecular drug D9ZQ7T
Mdam (Y-methylene-10-deazaaminopterin) . D0DO5J
Preclinical
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
1954u89 . D05HCO
Investigative
Click To Hide/Show 20 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Biopterin Small molecular drug DB03886
Piritrexim Small molecular drug DB03695
Sri-9439 Small molecular drug DB03351
Sri-9662 Small molecular drug DB03060
(2r6s)-6-{[Methyl(345-trimethoxyphenyl)Amino]Methyl}-125678-hexahydroquinazoline-24-diamine . DB08642
(4as)-5-[(24-diaminopteridin-6-yl)Methyl]-4a5-dihydro-2h-dibenzo[Bf]Azepin-8-ol . DB08448
24-diamino-5-(345-trimethoxy-benzyl)-pyrimidin-1-ium . DB03125
24-diamino-5-methyl-6-[(345-trimethoxy-n-methylanilino)Methyl]Pyrido[23-d]Pyrimidine . DB02104
24-diamino-6-[N-(2'5'-dimethoxybenzyl)-n-methylamino]Quinazoline . DB02427
24-diamino-6-[N-(3'4'5'-trimethoxybenzyl)-n-methylamino]Pyrido[23-d]Pyrimidine . DB02919
24-diamino-6-[N-(3'5'-dimethoxybenzyl)-n-methylamino]Pyrido[23-d]Pyrimidine . DB03987
5-[(3r)-3-(5-methoxy-2'6'-dimethylbiphenyl-3-yl)But-1-yn-1-yl]-6-methylpyrimidine-24-diamine . DB07144
5-[(3r)-3-(5-methoxy-3'5'-dimethylbiphenyl-3-yl)But-1-yn-1-yl]-6-methylpyrimidine-24-diamine . DB07142
5-[(3r)-3-(5-methoxy-4'-methylbiphenyl-3-yl)But-1-yn-1-yl]-6-methylpyrimidine-24-diamine . DB07141
5-[(3r)-3-(5-methoxybiphenyl-3-yl)But-1-yn-1-yl]-6-methylpyrimidine-24-diamine . DB07140
5-[3-(25-dimethoxyphenyl)Prop-1-yn-1-yl]-6-ethylpyrimidine-24-diamine . DB08234
6-(Octahydro-1h-indol-1-ylmethyl)Decahydroquinazoline-24-diamine . DB02559
N6-(25-dimethoxy-benzyl)-n6-methyl-pyrido[23-d]Pyrimidine-246-triamine . DB02583
Nicotinamide Adenine Dinucleotide Phosphate . DB03461
[N-(24-diaminopteridin-6-yl)-methyl]-dibenz[Bf]Azepine . DB08406
Discontinued
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Tnp-351 Small molecular drug D00CQW

References

1 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
2 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
3 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
4 Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors. J Am Chem Soc. 2022 Mar 30;144(12):5377-5388. doi: 10.1021/jacs.1c12748. Epub 2022 Mar 2.
5 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
6 Comprehensive Structure-Activity Profiling of Micheliolide and its Targeted Proteome in Leukemia Cells via Probe-Guided Late-Stage C-H Functionalization. ACS Cent Sci. 2021 May 26;7(5):841-857. doi: 10.1021/acscentsci.0c01624. Epub 2021 Apr 28.
Mass spectrometry data entry: PXD024455
7 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
8 Global targeting of functional tyrosines using sulfur-triazole exchange chemistry. Nat Chem Biol. 2020 Feb;16(2):150-159. doi: 10.1038/s41589-019-0404-5. Epub 2019 Nov 25.
9 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
10 Targeted Proteomic Approaches for Proteome-Wide Characterizations of the AMP-Binding Capacities of Kinases. J Proteome Res. 2022 Aug 5;21(8):2063-2070. doi: 10.1021/acs.jproteome.2c00225. Epub 2022 Jul 12.
11 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
12 Comparison of Quantitative Mass Spectrometry Platforms for Monitoring Kinase ATP Probe Uptake in Lung Cancer. J Proteome Res. 2018 Jan 5;17(1):63-75. doi: 10.1021/acs.jproteome.7b00329. Epub 2017 Nov 22.
Mass spectrometry data entry: PXD006095 , PXD006096
13 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
14 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
15 Solid Phase Synthesis of Fluorosulfate Containing Macrocycles for Chemoproteomic Workflows. bioRxiv [Preprint]. 2023 Feb 18:2023.02.17.529022. doi: 10.1101/2023.02.17.529022.
Mass spectrometry data entry: PXD039931
16 Tunable Amine-Reactive Electrophiles for Selective Profiling of Lysine. Angew Chem Int Ed Engl. 2022 Jan 26;61(5):e202112107. doi: 10.1002/anie.202112107. Epub 2021 Dec 16.
17 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
18 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
19 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
20 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
21 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
22 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570
23 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
24 Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening. J Am Chem Soc. 2019 Jun 5;141(22):8951-8968. doi: 10.1021/jacs.9b02822. Epub 2019 May 22.