PROTAC - Revision history

Jaime Prilusky at 05:27, 3 March 2021

2021-03-03T05:27:10Z

← Older revision		Revision as of 05:27, 3 March 2021
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			[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]
	A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.		A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.
	[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

	==PROTACpedia==		==PROTACpedia==
	[https://protacpedia.weizmann.ac.il/ PROTACpedia] <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). ~~The~~ search ~~can be performed~~ by various parameters such as Target name, UniProt ID, SMILES substructure or by ~~various~~ details regarding a publication or patent.		[https://protacpedia.weizmann.ac.il/ PROTACpedia] <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). Users can search PROTACpedia by various parameters such as Target name, UniProt ID, SMILES substructure or by details regarding a publication or patent.

	The [https://protacpedia.weizmann.ac.il/ptcb/stats statistics] page of PROTACpedia allows to overview current distribution on PROTACs of IC<sub>50</sub>, DC<sub>50</sub>, linker, etc.		The [https://protacpedia.weizmann.ac.il/ptcb/stats statistics] page of PROTACpedia allows to overview current distribution on PROTACs of IC<sub>50</sub>, DC<sub>50</sub>, linker, etc.

	{\| class="wikitable"		{\| class="wikitable"
			\|+PROTACs on PDB
			\|-
	\|- valign="top"		\|- valign="top"
	! PROTAC Target		! PROTAC Target
	! Structure		! 3D Structure
	\|- valign="top"		\|- valign="top"
	\| Bcl-Xl		\| Bcl-Xl

Jaime Prilusky at 05:16, 3 March 2021

2021-03-03T05:16:15Z

← Older revision		Revision as of 05:16, 3 March 2021
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	A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.		A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.
	[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]		[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

			==PROTACpedia==
			[https://protacpedia.weizmann.ac.il/ PROTACpedia] <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication or patent.

			The [https://protacpedia.weizmann.ac.il/ptcb/stats statistics] page of PROTACpedia allows to overview current distribution on PROTACs of IC<sub>50</sub>, DC<sub>50</sub>, linker, etc.

	{\| class="wikitable"		{\| class="wikitable"
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	==Predicting PROTAC-induced ternary complexes==		==Predicting PROTAC-induced ternary complexes==
	PRosettaC <ref>PRosettaC https://prosettac.weizmann.ac.il, a computational resource for the prediction of PROTAC-induced ternary complexes.</ref> is a computational resource for the prediction of PROTAC-induced ternary complexes <ref>pmid 32976709</ref>. PRosettaC receives as input, two protein structures (protein target and E3 ligase), including their appropriate ligands (binders), as well as the PROTAC chemical structure in a SMILES representation, and outputs predicted models for the ternary complex. Other methods become available <ref>pmid 32969649</ref><ref>pmid 33625214</ref>.		PRosettaC <ref>PRosettaC https://prosettac.weizmann.ac.il, a computational resource for the prediction of PROTAC-induced ternary complexes.</ref> is a computational resource for the prediction of PROTAC-induced ternary complexes <ref>pmid 32976709</ref>. PRosettaC receives as input, two protein structures (protein target and E3 ligase), including their appropriate ligands (binders), as well as the PROTAC chemical structure in a SMILES representation, and outputs predicted models for the ternary complex. Other methods become available <ref>pmid 32969649</ref><ref>pmid 33625214</ref>.

	~~==PROTACpedia==~~
	PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.

	== References ==		== References ==

Jaime Prilusky at 07:46, 1 March 2021

2021-03-01T07:46:44Z

← Older revision		Revision as of 07:46, 1 March 2021
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	! PROTAC Target		! PROTAC Target
	! Structure		! Structure
			\|- valign="top"
			\| Bcl-Xl
			\| [[6zhc]]
	\|- valign="top"		\|- valign="top"
	\| BRD4		\| BRD4
	\| [[6bn7]] [[6bn8]] [[6bn9]] [[6bnb]] [[6boy]] [[7khh]]		\| [[5t35]] [[6bn7]] [[6bn8]] [[6bn9]] [[6bnb]] [[6boy]] [[6sis]] [[7khh]]
	\|- valign="top"		\|- valign="top"
	\| BTK		\| BTK
	\| [[6w7o]] [[6w8i]]		\| [[6w7o]] [[6w8i]]
	~~\|- valign="top"~~
	~~\| VHL~~
	~~\| [[5t35]] [[6sis]] [[6zhc]]~~
	\|- valign="top"		\|- valign="top"
	\| SMARCA2		\| SMARCA2

Jaime Prilusky at 07:32, 1 March 2021

2021-03-01T07:32:57Z

← Older revision		Revision as of 07:32, 1 March 2021
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	! Structure		! Structure
	\|- valign="top"		\|- valign="top"
	\| ~~BRAF kinase domain~~		\| BRD4
	\| [[~~6uuo~~]]		\| [[6bn7]] [[6bn8]] [[6bn9]] [[6bnb]] [[6boy]] [[7khh]]
	\|- valign="top"		\|- valign="top"
	\| ~~BRD9 bromodomain~~		\| BTK
	\| [[~~6hm0~~]]		\| [[6w7o]] [[6w8i]]
	\|- valign="top"		\|- valign="top"
	\| ~~Cereblon~~		\| VHL
	\| [[~~6r0q~~]], [[~~6r0u~~]], [[~~6r0v]], [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x~~]]		\| [[5t35]] [[6sis]] [[6zhc]]
	\|- valign="top"		\|- valign="top"
	\| ~~DDB1-CRBN-BRD4(BD1)~~		\| SMARCA2
	\| [[~~6bn7]], [[6bn8]], [[6bn9]], [[6bnb~~]], [[~~6boy~~]]		\| [[6hax]] [[6hay]] [[6hr2]]
	~~\|- valign="top"~~
	~~\| SMARCA2, SMARCA4~~
	\| [[6hr2]]
	\|}		\|}

Jaime Prilusky at 07:15, 1 March 2021

2021-03-01T07:15:11Z

← Older revision		Revision as of 07:15, 1 March 2021
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	~~<StructureSection load='' size='340' side='right' caption='' scene='87/876131/5t35/2'>~~
	A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.		A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.
			[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

	{\| class="wikitable"		{\| class="wikitable"
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	==PROTACpedia==		==PROTACpedia==
	~~[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [~~https://protacpedia.weizmann.ac.il/~~ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533~~. ~~<span class="bg-lightblue"><b>target binding ligand</b>~~</~~span~~>~~<span class="bg~~-~~lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]~~		PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.

	PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.
	~~</StructureSection>~~
	== References ==		== References ==
	<references/>		<references/>

	[[Category:Protac]]		[[Category:Protac]]

Jaime Prilusky at 18:55, 28 February 2021

2021-02-28T18:55:35Z

← Older revision		Revision as of 18:55, 28 February 2021
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	==PROTACpedia==		==PROTACpedia==
	[[Image:PROTAC_70.png\|thumb\|right\|~~300px~~\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]		[[Image:PROTAC_70.png\|thumb\|right\|200px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

	PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.		PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.

Jaime Prilusky at 16:39, 28 February 2021

2021-02-28T16:39:39Z

← Older revision		Revision as of 16:39, 28 February 2021
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	{\| class="wikitable"		{\| class="wikitable"
	\|-		\|- valign="top"
	! PROTAC Target		! PROTAC Target
	! Structure		! Structure
	\|-		\|- valign="top"
	\| BRAF kinase domain		\| BRAF kinase domain
	\| [[6uuo]]		\| [[6uuo]]
	\|-		\|- valign="top"
	\| BRD9 bromodomain		\| BRD9 bromodomain
	\| [[6hm0]]		\| [[6hm0]]
	\|-		\|- valign="top"
	\| Cereblon		\| Cereblon
	\| [[6r0q]], [[6r0u]], [[6r0v]], [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x]]		\| [[6r0q]], [[6r0u]], [[6r0v]], [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x]]
	\|-		\|- valign="top"
	\| DDB1-CRBN-BRD4(BD1)		\| DDB1-CRBN-BRD4(BD1)
	\| [[6bn7]], [[6bn8]], [[6bn9]], [[6bnb]], [[6boy]]		\| [[6bn7]], [[6bn8]], [[6bn9]], [[6bnb]], [[6boy]]
	\|-		\|- valign="top"
	\| SMARCA2, SMARCA4		\| SMARCA2, SMARCA4
	\| [[6hr2]]		\| [[6hr2]]

Jaime Prilusky at 16:29, 28 February 2021

2021-02-28T16:29:59Z

← Older revision		Revision as of 16:29, 28 February 2021
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	~~<!--~~ <StructureSection load='' size='340' side='right' caption='' scene='87/876131/~~Protac~~/1'> ~~-->~~		<StructureSection load='' size='340' side='right' caption='' scene='87/876131/5t35/2'>
	[[Image:PROTAC_70.png\|thumb\|right\|300px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

	A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.		A Proteolysis-Targeting Chimera (PROTAC) is a small protein with two active domains joined by a linker. PROTACs represent an alternative to conventional enzyme inhibitors, by enabling [[Proteasome\|proteasome]] induced degradation of the target protein <ref>pmid 28288108</ref>.

Line 29:		Line 27:

	==PROTACpedia==		==PROTACpedia==
			[[Image:PROTAC_70.png\|thumb\|right\|300px\|Representative PROTAC from [https://protacpedia.weizmann.ac.il/ptcb/detp?i=70 PROTACpedia] targeting EGFR Epidermal growth factor receptor P00533. <span class="bg-lightblue"><b>target binding ligand</b></span><span class="bg-lightmagenta"><b>linker</b></span><span class="bg-lightgreen"><b>E3 binder</b></span>]]

	PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.		PROTACpedia <ref>PROTACpedia https://protacpedia.weizmann.ac.il/, a resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs).</ref> is a collaborative and comprehensive, high-quality and freely accessible resource of manually curated data on Proteolysis Targeting Chimeras (PROTACs). The search can be performed by various parameters such as Target name, UniProt ID, SMILES substructure or by various details regarding a publication.
	~~<!--~~ </StructureSection~~> --~~>		</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

	[[Category:Protac]]		[[Category:Protac]]

Jaime Prilusky at 16:00, 28 February 2021

2021-02-28T16:00:00Z

← Older revision		Revision as of 16:00, 28 February 2021
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	\| BRAF kinase domain		\| BRAF kinase domain
	\| [[6uuo]]		\| [[6uuo]]
			\|-
			\| BRD9 bromodomain
			\| [[6hm0]]
	\|-		\|-
	\| Cereblon		\| Cereblon
	\| [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x]]		\| [[6r0q]], [[6r0u]], [[6r0v]], [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x]]
	\|-		\|-
	\| DDB1-CRBN-BRD4(BD1)		\| DDB1-CRBN-BRD4(BD1)
	\| [[6bn7]], [[6bn8]], [[6bn9]], [[6bnb]], [[6boy]]		\| [[6bn7]], [[6bn8]], [[6bn9]], [[6bnb]], [[6boy]]
			\|-
			\| SMARCA2, SMARCA4
			\| [[6hr2]]
	\|}		\|}


	==Predicting PROTAC-induced ternary complexes==		==Predicting PROTAC-induced ternary complexes==

Jaime Prilusky at 15:51, 28 February 2021

2021-02-28T15:51:34Z

← Older revision		Revision as of 15:51, 28 February 2021
Line 13:		Line 13:
	\|-		\|-
	\| Cereblon		\| Cereblon
	\| [[6r1k]]		\| [[6r11]], [[6r12]], [[6r13]], [[6r18]], [[6r19]], [[6r1a]], [[6r1c]], [[6r1d]], [[6r1k]], [[6r1w]], [[6r1x]]
	\|-		\|-
	\| DDB1-CRBN-BRD4(BD1)		\| DDB1-CRBN-BRD4(BD1)
	\| [[6bn7]],[[6bn8]],[[6bn9]],[[6bnb]],[[6boy]]		\| [[6bn7]], [[6bn8]], [[6bn9]], [[6bnb]], [[6boy]]
	\|}		\|}