SAR Table 2Pyrazol-5-yl-isoxazole Scaffold

Compound InformationHTS AssaysProbe Development Assays
CompoundSR-NumberStructureSolubility in PBS (μM)Solubility in PBS-6% FBS (μM)CIDSIDMLSVendorVendor Catalog IDAID 1448: TRPML3 Primary 1X%ACTAID 1424: TRPN1 Primary 1X%ACTAID 1526: TRPML3 CRUN 3X%ACTAID 1525: TRPN1 3X%ACTTRPN1 CS DRUN (AID 1682) EC50, μMAID 2510: TRPML3 EC50, μMAID 2583: TRPN1 EC50,AID 2694: TRPML3 Patch Clamp: nA/pF, −80 mVAID 2692: TRPN1 Patch Clamp: nA/pF, −80 mVAID 2719: TRPML3 Fura-2 Imaging: ΔF, 340 nm/380 nMAID 2770: Fura-2 Assay: Other channels DF340/F380AID 602128: TRPML3 EC50, μMAID 602129: TRPML3 EC50, μM
Probe 2 Compound (6a) (this liquid SID is associated with an incorrect CID structure in PubChem).SR-01000768170-1
Image ml269fu24.jpg
0.15.9274558326731169MLS 001111122MaybridgeSPB 04991Active (81.8)Inactive (1.01)Active (106.23)Inactive (0.49Inactive (>29.9)Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Probe 2 (this powder SID was purchased to confirm activity; SID is associated with an incorrect CID structure in PubChem)SR-01000768170-2
Image ml269fu24.jpg
274558387692372NoneMaybridgeSPB 04991Not tested: this SID is a powder and was not tested during HTS0.2526 (Active)>29.9 (Inactive)−0.14 ±0.02 (Active)−0.004 ±0.001 (Inactive)0.72 ±0.05 (Active)0.005 ± 0.002 (Inactive)SID Not TestedSID Not Tested
Probe 2 (this powder SID was synthesized to prove that the CID structure in PubChem is incorrect; compound is inactive)SR-01000768170-3
Image ml269fu24.jpg
0.02122745583124349366NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound was synthesized after these assays were completed.>29.9 (Inactive)SID Not Tested
Probe 2 (ML269) Compound (6a) (this powder was synthesized to prove SAR; compound associated with this structure is active. Note new CID).SR-03000002360-1
Image ml269fu25.jpg
53239838124349367MLS003675345TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.0.291 (Active)SID Not Tested
Compound InformationHTS AssaysProbe Development Assays
CompoundSR-NumberStructureCIDSIDMLSVendorVendor Catalog IDAID 1448: TRPML3 Primary 1X%ACTAID 1424: TRPN1 Primary 1X%ACTAID 1526: TRPML3 CRUN 3X%ACTAID 1525: TRPN1 3X%ACTAID 1562: TRPML3 EC50, μMTRPN1 CS DRUN (AID 1682) EC50, μMAID 2510: TRPML3 EC50, μMAID 2583: TRPN1 EC50,AID 2694:TRPML3 Patch Clamp: nA/pF, −80 mVAID 2692: TRPN1 Patch Clamp: nA/pF, −80 mVAID 2719:TRPML3 Fura-2 Imaging: ΔF, 340 nm/380 nMAID 2770: Fura-2 Assay: Other channels DF340/F380AID 602128: TRPML3 EC50, μMAID 602129: TRPML3 EC50, μM
Analog 1aSR-03000002573-1
Image ml269fu26.jpg
53384691125311254MLS003875016TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.1.459 (Active)
Analog 1b (MLSMR liquid SID is associated with incorrect structure in PubChem)SR-01000767070-1
Image ml269fu27.jpg
274560026731235MLS 001111124MaybridgeSPB 05016119.6Inactive (1.19)Active (94.33)Inactive (−1.09Active (0.819)Inactive (>29.9)Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Analog 1b (this sample was purchased to confirm HTS activity)SR-01000767070-2
Image ml269fu27.jpg
274560087692371NoneMaybridgeSPB 05016Not tested: this SID is a powder and was not tested during HTS1.005 (Active)>29.9 (Inactive)This SID not tested in these assays
Analog 1b (this sample was synthesized to obtain correct structure shown)SR-03000002582-1
Image ml269fu28.jpg
2745600125311263NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSCompound was synthesized in order to confirm the structure was incorrect in PubChem.>29.9 (Inactive)
Analog 2aSR-03000002574-1
Image ml269fu29.jpg
53384705125311255NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.3.336 (Active)
Analog 2b (MLSMR liquid SID is associated with an incorrect structure in PubChem)SR-01000767049-1
Image ml269fu30.jpg
274559826731234MLS 001111123MaybridgeSPB 0501333.0Inactive (1.49)Active (51.03)Inactive (−0.27Active (4.26)Inactive (>29.9)Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Analog 2b (this sample was synthesized to obtain correct structure shown)SR-03000002583-1
Image ml269fu31.jpg
2745598125311264NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 3aSR-03000002576-1
Image ml269fu32.jpg
53384724125311257NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 3b (MLSMR SID is associated with an incorrect structure in PubChem)SR-01000631911-2
Image ml269fu33.jpg
274560126731237MLS 001111125MaybridgeSPB 05017Inactive (8.45)Inactive (2.08)Not tested due to lack of TRPML3 activity in HTS Primary assay.Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Analog 3b (this sample was synthesized to obtain correct structure shown)SR-03000002584-1
Image ml269fu34.jpg
2745601125311265NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 4aSR-03000002575-1
Image ml269fu35.jpg
53384697125311256NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.15.82 (Inactive)
Analog 4b (the MLSMR liquid SID is associated with an incorrect structure in PubChem)SR-01000773206-1
Image ml269fu36.jpg
274558226731233MLS 001111121MaybridgeSPB 04990Inactive (3.88)Inactive (0.14)Not tested due to lack of TRPML3 activity in HTS Primary assay.Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Analog 4b (this sample was synthesized to obtain correct structure shown)SR-03000002585-1
Image ml269fu37.jpg
2745582125311266NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 5 (MLSMR Liquid)SR-01000761039-1
Image ml269fu38.jpg
274556726729029MLS 000834032MaybridgeSPB 04969Inactive (−1.12)Inactive (−1.49)Not tested due to lack of TRPML3 activity in HTS Primary assay.Not tested: this SID is an MLSMR liquid and was not tested during MedChem
Analog 5 (synthesized)SR-03000002361-1
Image ml269fu39.jpg
2745567124349368NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)Not tested
Analog 6SR-03000002577-1
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53384721125311258NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.2.988 (Active)
Analog 7SR-03000002578-1
Image ml269fu41.jpg
53384692125311259MLS003875015TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.0.68 (Active)
Analog 8SR-03000002580-1
Image ml269fu42.jpg
53384707125311261NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 9SR-03000002581-1
Image ml269fu43.jpg
53384683125311262NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 10SR-03000002579-1
Image ml269fu44.jpg
53384703125311260NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 11SR-03000002564-1
Image ml269fu45.jpg
53384708125311245NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.4.89 (Active)
Analog 12SR-03000002565-1
Image ml269fu46.jpg
53384678125311246MLS003875018TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.1.945 (Active)
Analog 13SR-03000002566-1
Image ml269fu47.jpg
53384730125311247MLS003875019TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.2.386 (Active)
Analog 14SR-03000002567-1
Image ml269fu48.jpg
53384702125311248NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.3.78 (Active)
Analog 15SR-03000002568-1
Image ml269fu49.jpg
53384723125311249NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 16SR-03000002569-1
Image ml269fu50.jpg
53384713125311250NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)
Analog 17SR-03000002570-1
Image ml269fu51.jpg
53384729125311251MLS003875017TSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.1.533 (Active)
Analog 18SR-03000002571-1
Image ml269fu52.jpg
53384687125311252NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.3.576 (Active)
Analog 19SR-03000002572-1
Image ml269fu53.jpg
53384682125311253NoneTSRINoneNot tested: this SID is a powder and was not tested during HTSNot tested: Compound synthesized after these assays were completed.>29.9 (Inactive)

From: Identification of Selective Agonists of the Transient Receptor Potential Channels 3 (TRPML3)

Cover of Probe Reports from the NIH Molecular Libraries Program
Probe Reports from the NIH Molecular Libraries Program [Internet].

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