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PROTAC

E3 Ligase Ligand-Linker Conjugate

(67)

Ligand for E3 Ligase

(21)

Ligand for Target Protein for PROTAC

PROTAC-linker Conjugate for PAC

(2)

SNIPER

(25)

Target Protein Ligand-Linker Conjugate

(9)

SNIPER

"IAPs can inhibit apoptosis by inhibiting caspase, and also exhibits the activity of E3 ubiquitin ligase. Specific and nongenetic IAP-based protein erasers (SNIPERs) are hybrid molecules that designed based on IAPs, and used to degrade the target proteins closely associated with diseases. SNIPERs (PROTACs) degrade diseases-associated proteins through human inherent ubiquitin-proteasome system. So far, many SNIPERs have been developed to treat diseases that difficult to handle by traditional methods, such as radiotherapy, chemotherapy and small molecule inhibitors, and showed promising prospects in application. PROTACs/SNIPERs are composed of three parts, including a ligand for target protein, a ligand for E3 ligase and a linker between them. All three parts are crucial for protein degradation activity of PROTACs/SNIPERs. In recent years, PROTACs (SNIPERs) have been universally used as inducers to degrade many target proteins, such as AR, ER, Era and etc."

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PROTAC AR Degrader-4

T185961351169-31-7

PROTAC AR Degrader-4 comprises a cIAP1 ligand binding group, a linker, and an androgen receptor (AR) binding group. It is an AR degrader and is considered a specific and non-genetic IAP-dependent protein eraser (SNIPER) [1].

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SNIPER(ABL)-015

T18685

SNIPER(ABL)-015, a compound that conjugates GNF5 (ABL inhibitor) to MV-1 (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels with a DC50 of 5 μM [1].

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PROTAC ERα Degrader-2

T186051351169-29-3

PROTAC ERα Degrader-2 is composed of a cIAP1 ligand binding group, a linker, and an estrogen receptor α (ERα) binding group, serving as an ERα degrader. It achieves maximal ERα degradation in human mammary tumor MCF7 cells at a concentration of 30 μM. Degradation inducers that utilize cIAP1 are referred to as specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

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SNIPER(ABL)-039

T186902222354-29-0

SNIPER(ABL)-039, conjugating Dasatinib (ABL inhibitor) to an LCL161 derivative (IAP ligand) with a linker, induces the reduction of BCR-ABL protein with a DC50 of 10 nM. IC50s are 0.54 nM for ABL, 10 nM for cIAP1, 12 nM for cIAP2, and 50 nM for XIAP[1].

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SNIPER(ABL)-024

T186882222355-77-1

SNIPER(ABL)-024, a compound that conjugates GNF5 (ABL inhibitor) to an LCL161 derivative (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels, achieving a half-maximal degradation concentration (DC50) of 5μM[1].

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SNIPER(ABL)-013

T18684

SNIPER(ABL)-013, a compound that links GNF5 (ABL inhibitor) with Bestatin (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels with a DC50 of 20 μM[1].

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SNIPER(ABL)-033

T186892222354-18-7

SNIPER(ABL)-033, a compound that conjugates HG-7-85-01 (ABL inhibitor) to a LCL161 derivative (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels, exhibiting a DC50 of 0.3 μM[1].

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SNIPER(ABL)-047

T18692

SNIPER(ABL)-047, a compound that links HG-7-85-01 (an ABL inhibitor) to MV-1 (an IAP ligand) via a linker, effectively decreases the BCR-ABL protein levels, achieving a DC50 value of 2 μM[1].

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PROTAC CRABP-II Degrader-2

T138371225383-38-9

PROTAC CRABP-II Degrader-2 is a potent cIAp1-based degrader of cellular retinoic acid binding protein (CRABP-II).

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SNIPER(ABL)-058

T186952222354-61-0

SNIPER(ABL)-058, a compound that links Imatinib (ABL inhibitor) with a derivative of LCL161 (IAP ligand) through a linker, effectively decreases BCR-ABL protein levels, achieving a half-maximal degradation concentration (DC50) of 10 μM[1].

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SNIPER(ER)-110

T18696

SNIPER(ER)-110 comprises a cIAP1 ligand and an estrogen ligand connected by a linker. SNIPER(ER)-51 induces estrogen receptor (ER) protein degradation with DC50s of <3 nM and 7.7 nM after 4 h and 48 h, respectively [1].

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SNIPER(ABL)-050

T18694

SNIPER(ABL)-050 is a chemical compound that combines Imatinib, an ABL inhibitor, with MV-1, an IAP ligand, using a linker. This conjugation results in the reduction of BCR-ABL protein[1].

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SNIPER(ABL)-019

T18686

SNIPER(ABL)-019, a compound that links Dasatinib (ABL inhibitor) to MV-1 (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels, exhibiting a DC50 of 0.3 μM[1].

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SNIPER(ABL)-044

T18691

SNIPER(ABL)-044, a compound that links HG-7-85-01 (ABL inhibitor) to Bestatin (IAP ligand) via a linker, effectively reduces BCR-ABL protein levels, achieving a DC50 value of 10 μM[1].

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BzNH-BS

T17706

BzNH-BS is a chemical compound comprising two distinct ligands: methyl-bestatin (MeBS) for cIAP1 and benzoyl-amide. The ligands are interconnected through linkers. MeBS functions as a ligand for cIAP1, a ubiquitin ligase involved in cellular inhibition of apoptosis processes [1].

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SNIPER(ABL)-049

T18693

SNIPER(ABL)-049, a compound that conjugates Imatinib (ABL inhibitor) with Bestatin (IAP ligand) through a linker, effectively reduces BCR-ABL protein levels, demonstrating a DC50 of 100 μM[1].

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PROTAC RAR Degrader-1

T186351351169-27-1

PROTAC RAR Degrader-1, an RAR degrader, consists of a cIAP1 ligand binding group, a linker, and an RAR ligand binding group. It achieves maximal RAR degradation at a concentration of 30 μM in HT1080 cells. Degradation inducers that utilize cIAP1 are known as specific and non-genetic IAP-dependent protein erasers (SNIPERs)[1].

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SNIPER(TACC3)-1

T13891

SNIPER(TACC3)-1 targets TACC3 protein degradation via the ubiquitin-proteasome pathway.It induces cancer cell death.

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SNIPER(TACC3)-2

T13892

SNIPER(TACC3)-2 targets TACC3 protein degradation via the ubiquitin-proteasome pathway. It induces cancer cell death.

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Biotin-BS

T17545

Biotin-BS is a chemical compound composed of two distinct ligands: methyl-bestatin (MeBS) for cIAP1 and biotin. These ligands are interconnected through linkers. MeBS serves as a ligand specifically for the cellular inhibitor of apoptosis protein 1 (cIAP1) ubiquitin ligase[1].

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SNIPER(ER)-87

T186972222354-91-6

SNIPER(ER)-87 is a chemical compound composed of a derivative of the inhibitor of apoptosis protein (IAP) ligand LCL161 conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen using a PEG linker. It effectively degrades the ERα protein with an IC50 value of 0.097 μM. Within cells, SNIPER(ER)-87 selectively recruits XIAP to ERα, and XIAP functions as the primary E3 ubiquitin ligase responsible for the degradation of ERα induced by SNIPER(ER)-87[1][2].

$1,980

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PROTAC CRABP-II Degrader-3

T138381225383-41-4

PROTAC CRABP-II Degrader-3 is a potent degrader of cellular retinoic acid binding protein (CRABP-II) based on [cIAp1].

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SNIPER(ABL)-020

T18687

SNIPER(ABL)-020 is a chemical compound consisting of Dasatinib, an ABL inhibitor, and Bestatin, an IAP ligand, conjugated with a linker. This compound effectively reduces the BCR-ABL protein[1].

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SNIPER(BRD)-1

T169052095244-54-3

SNIPER(BRD)-1 is a chemical compound composed of a derivative of the IAP antagonist LCL-161 and the BET inhibitor (+)-JQ-1, linked together. It promotes the degradation of BRD4 through the ubiquitin-proteasome pathway and effectively degrades cIAP1, cIAP2, and XIAP with IC50 values of 6.8 nM, 17 nM, and 49nM, respectively[1].