Selpercatinib

Summary

Selpercatinib (CHEMBL4559134) is an approved small molecule (ATC L01EX22) targeting RET; indicated across 10 conditions including non-small cell lung carcinoma and neoplasm; with CIViC clinical evidence for 31 variant-indication associations (e.g. RET Fusion in lung non-small cell carcinoma).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L01EX22
• Targets: 1 (RET)
• Indications: 10 conditions
• Clinical trials: 36
• Precision-oncology evidence (CIViC): 31 variant–indication associations
• Chemistry: 525.6 Da · C29H31N7O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4559134
Name	Selpercatinib
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	134436906
ATC	L01EX22
Molecular formula	C29H31N7O3
Molecular weight	525.6
InChIKey	XIIOFHFUYBLOLW-UHFFFAOYSA-N

SMILES: CC(C)(COC1=CN2C(=C(C=N2)C#N)C(=C1)C3=CN=C(C=C3)N4CC5CC(C4)N5CC6=CN=C(C=C6)OC)O

IUPAC name: 6-(2-hydroxy-2-methylpropoxy)-4-[6-[6-[(6-methoxy-3-pyridinyl)methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl]-3-pyridinyl]pyrazolo[1,5-a]pyridine-3-carbonitrile

Also known as: Loxo-292, LOXO-292, LY-3527723, LY3527723, Ret inhibitor loxo-292, Retevmo, Retsevmo, Selpercatinib, SELPERCATINIB

Patent coverage: 656 distinct patent families (1,409 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,277 (91%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
RET	ret proto-oncogene	Inhibition	7.85	0.4%	P07949

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: Proto-oncogene tyrosine-protein kinase receptor Ret, Vascular endothelial growth factor receptor 2.

Bioactivity

ChEMBL activities: 31 potent at pChembl ≥ 5 of 31 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
RET	10	IC50	0.1	nM	CHEMBL_ACT_29235488
RET	9.75	IC50	0.18	nM	CHEMBL_ACT_29146647
RET	9.52	IC50	0.3	nM	CHEMBL_ACT_29235523
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_24867232
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_25016240
RET	9.4	IC50	0.4	nM	CHEMBL_ACT_25935703
RET	9.38	IC50	0.42	nM	CHEMBL_ACT_24867237
RET	9.38	IC50	0.42	nM	CHEMBL_ACT_25016242
RET	9.15	IC50	0.7	nM	CHEMBL_ACT_24867247
RET	9.1	IC50	0.8	nM	CHEMBL_ACT_25016244
RET	8.91	IC50	1.24	nM	CHEMBL_ACT_24419670
RET	8.68	IC50	2.1	nM	CHEMBL_ACT_29235586
RET	8.64	IC50	2.3	nM	CHEMBL_ACT_29119327
RET	8.55	IC50	2.8	nM	CHEMBL_ACT_25061386
RET	8.44	IC50	3.6	nM	CHEMBL_ACT_29235453
RET	7.85	IC50	14	nM	CHEMBL_ACT_26998390
RET	7.85	IC50	14	nM	CHEMBL_ACT_27031706
RET	7.85	IC50	14	nM	CHEMBL_ACT_27874016
RET	7.85	IC50	14	nM	CHEMBL_ACT_28281512
RET	7.82	IC50	15.1	nM	CHEMBL_ACT_26998450
RET	7.62	IC50	24.1	nM	CHEMBL_ACT_27031709
RET	7.62	IC50	24.1	nM	CHEMBL_ACT_27874019
RET	7.62	IC50	24.1	nM	CHEMBL_ACT_28281515
RET	7.53	IC50	29.3	nM	CHEMBL_ACT_26998399
RET	7.02	IC50	95.3	nM	CHEMBL_ACT_29235588
KDR	7	IC50	100	nM	CHEMBL_ACT_24867252
RET	6.97	IC50	107.3	nM	CHEMBL_ACT_29235590
RET	6.61	IC50	244.1	nM	CHEMBL_ACT_29235558
RET	6.28	IC50	531	nM	CHEMBL_ACT_27031712
RET	6.28	IC50	531	nM	CHEMBL_ACT_27874022
RET	6.28	IC50	531	nM	CHEMBL_ACT_28281518

Target pathways

Aggregated over 1 target gene(s): RET.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
RAF/MAP kinase cascade	1	RET
RET signaling	1	RET
NPAS4 regulates expression of target genes	1	RET
Formation of the nephric duct	1	RET
Formation of the ureteric bud	1	RET

Dominant GO biological processes

GO term	Targets
MAPK cascade	1
ureteric bud development	1
neural crest cell migration	1
embryonic epithelial tube formation	1
homophilic cell-cell adhesion	1
neuron cell-cell adhesion	1
signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
axon guidance	1
posterior midgut development	1
positive regulation of gene expression	1
positive regulation of neuron projection development	1
regulation of cell adhesion	1
positive regulation of cell migration	1
membrane protein proteolysis	1

Indications & clinical

Indications

4 approved indications. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
non-small cell lung carcinoma	4	MONDO:0005233	EFO:0003060
neoplasm	4	MONDO:0005070	EFO:0000616
thyroid gland papillary carcinoma	4	MONDO:0005075	EFO:0000641
thyroid tumor	4	MONDO:0015074	EFO:0003841

3 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
thyroid gland follicular carcinoma	2	MONDO:0005034	EFO:0000501
liver disorder	1	MONDO:0005154	EFO:0001421
kidney failure	1	MONDO:0001106	HP:0000083

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 36.

Phase distribution

Phase	Trials
PHASE1	15
PHASE2	11
PHASE3	3
Not specified	3
PHASE1/PHASE2	2
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07010393	PHASE4	NOT_YET_RECRUITING	Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study
NCT04194944	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
NCT04211337	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer
NCT04819100	PHASE3	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)
NCT02925234	PHASE2	RECRUITING	The Drug Rediscovery Protocol (DRUP Trial)
NCT03155620	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03157128	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)
NCT03899792	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors
NCT03944772	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)
NCT04268550	PHASE2	ACTIVE_NOT_RECRUITING	Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial)
NCT04280081	PHASE2	ACTIVE_NOT_RECRUITING	A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation
NCT04320888	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04759911	PHASE2	ACTIVE_NOT_RECRUITING	Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer
NCT05668962	PHASE2	RECRUITING	Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC
NCT06458036	PHASE2	RECRUITING	Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)
NCT04591431	PHASE2	UNKNOWN	The Rome Trial From Histology to Target: the Road to Personalize Target Therapy and Immunotherapy
NCT05364645	PHASE2	WITHDRAWN	Testing the Use of Targeted Treatment for RET Positive Advanced Non-small Cell Lung Cancer
NCT04782076	PHASE1	COMPLETED	A Drug Drug Interaction (DDI) Study of Selpercatinib and Dabigatran in Healthy Participants
NCT05089019	PHASE1	COMPLETED	A Study Comparing Two Formulations of Selpercatinib (LY3527723) in Healthy Participants
NCT05136404	PHASE1	COMPLETED	A Relative Bioavailability Study of Selpercatinib (LY3527723) in Healthy Participants
NCT05324124	PHASE1	COMPLETED	A Study of the Effect of Food on Selpercatinib (LY3527723) in Healthy Participants
NCT05338476	PHASE1	COMPLETED	A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants
NCT05338489	PHASE1	COMPLETED	A Study of Effects of Itraconazole and Rifampin on Selpercatinib (LY3527723) in Healthy Participants
NCT05338502	PHASE1	COMPLETED	Study of H2 Antagonist and a Proton Pump Inhibitor of Selpercatinib in Healthy Participants
NCT05338515	PHASE1	COMPLETED	A Study of Selpercatinib (LY3527723) in Healthy Participants
NCT05436912	PHASE1	COMPLETED	A Study of Effects of Selpercatinib in Hepatically Impaired Participants and Healthy Participants
NCT05468164	PHASE1	COMPLETED	A Study of Effect of Food and a Proton Pump Inhibitor on Selpercatinib (LY3527723) in Healthy Participants
NCT05469100	PHASE1	COMPLETED	A Study of Effect of Selpercatinib (LY3527723) in Participants With Normal and Impaired Renal Function
NCT05469113	PHASE1	COMPLETED	A Study of Effects of Selpercatinib (LY3527723) on Repaglinide in Healthy Participants
NCT05630274	PHASE1	COMPLETED	A Study of Effect of Selpercatinib (LY3527723) on Corrected QT (QTc) Interval in Healthy Participants
NCT05630287	PHASE1	COMPLETED	A Study of Absorption, Metabolism, Excretion, and Absolute Bioavailability of Carbon-14-Labelled [14C] Selpercatinib (LY3527723) in Healthy Male Participants
NCT05906836	PHASE1	COMPLETED	A Drug Drug Interaction (DDI) Study of Selpercatinib (LY3527723) and Rosuvastatin in Healthy Participants
NCT07146893	EARLY_PHASE1	NOT_YET_RECRUITING	Feasibility Study for Repurposing RET Inhibitors
NCT06532149	Not specified	RECRUITING	ERectile Dysfunctions, gOnadotoxicity and Sexual Health Assessment in Men With Lung Cancer
NCT03906331	Not specified	APPROVED_FOR_MARKETING	Expanded Access for the Treatment of Cancers With Rearranged During Transfection (RET) Activation
NCT07543887	Not specified	COMPLETED	Selpercatinib and Body Composition

Clinical evidence (CIViC)

Variant × indication × effect (31 predictive associations from 40 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
RET Fusion	Lung Non-small Cell Carcinoma	Sensitivity/Response	Selpercatinib	CIViC A	EID11318 +3
RET Mutation	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC A	EID12157 +2
RET Fusion OR RET Mutation	Solid Tumor	Sensitivity/Response	Selpercatinib	CIViC A	EID12056 +1
RET Fusion	Thyroid Cancer	Sensitivity/Response	Selpercatinib	CIViC A	EID8852
RET M918T	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC A	EID12598
RET E632_L633del	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC B	EID11875 +2
KIF5B::RET Fusion	Lung Cancer	Sensitivity/Response	Selpercatinib	CIViC B	EID7067
RET Fusion	Solid Tumor	Sensitivity/Response	Selpercatinib	CIViC B	EID12134
RET Fusion	Papillary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC B	EID7069
RET V804M	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC C	EID6951 +1
KIF5B::RET Fusion	Lung Non-small Cell Carcinoma	Sensitivity/Response	Selpercatinib	CIViC C	EID6948
RET D378_G685>E	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC C	EID11658
RET M918T AND RET V804M	Medullary Thyroid Carcinoma	Sensitivity/Response	Selpercatinib	CIViC C	EID6950
KIF5B::RET Fusion AND ( RET G810C OR RET G810S OR RET G810R )	Lung Non-small Cell Carcinoma	Resistance	Selpercatinib	CIViC C	EID8195
KIF5B::RET Fusion AND RET G810S	Lung Non-small Cell Carcinoma	Resistance	Selpercatinib	CIViC C	EID12496
RET G810C	Cancer	Resistance	Pralsetinib + Selpercatinib	CIViC C	EID8918
RET G810S	Medullary Thyroid Carcinoma	Resistance	Pralsetinib + Selpercatinib	CIViC C	EID8919
RET M918T AND RET G810S	Medullary Thyroid Carcinoma	Resistance	Selpercatinib	CIViC C	EID8196
RET Y806C	Medullary Thyroid Carcinoma	Resistance	Pralsetinib + Selpercatinib	CIViC C	EID8920
RET Y806N	Medullary Thyroid Carcinoma	Resistance	Pralsetinib + Selpercatinib	CIViC C	EID8921
KIF5B::RET Fusion	Cancer	Sensitivity/Response	Selpercatinib	CIViC D	EID12814
RET C618R	Cancer	Sensitivity/Response	Selpercatinib	CIViC D	EID11877
RET D898_E901del	Cancer	Sensitivity/Response	Pralsetinib + Selpercatinib	CIViC D	EID11870
RET E632_L633del	Cancer	Sensitivity/Response	Selpercatinib	CIViC D	EID12712
RET Fusion	Cancer	Sensitivity/Response	Selpercatinib	CIViC D	EID6949
RET M918T	Cancer	Sensitivity/Response	Pralsetinib + Selpercatinib	CIViC D	EID11867
RET M918T	Cancer	Sensitivity/Response	Selpercatinib	CIViC D	EID11876
RET T930K	Cancer	Sensitivity/Response	Pralsetinib + Selpercatinib	CIViC D	EID11869
RET T930P	Cancer	Sensitivity/Response	Pralsetinib + Selpercatinib	CIViC D	EID11868
RET E632_L633del	Cancer	Resistance	Selpercatinib + Pralsetinib	CIViC D	EID12715

+1 more predictive associations (showing top 30 by level).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

109 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	RET
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	RET
FOSTAMATINIB	ChEMBL + PubChem	Phase 4 (approved)	RET
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	RET
PAZOPANIB	ChEMBL + PubChem	Phase 4 (approved)	RET
REGORAFENIB	ChEMBL + PubChem	Phase 4 (approved)	RET
ALECTINIB	ChEMBL	Phase 4 (approved)	RET
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	RET
AXITINIB	ChEMBL	Phase 4 (approved)	RET
BARICITINIB	ChEMBL	Phase 4 (approved)	RET
BOSUTINIB	ChEMBL	Phase 4 (approved)	RET
BRIGATINIB	ChEMBL	Phase 4 (approved)	RET
CABOZANTINIB	ChEMBL	Phase 4 (approved)	RET
CAPIVASERTIB	ChEMBL	Phase 4 (approved)	RET
CERITINIB	ChEMBL	Phase 4 (approved)	RET
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	RET
DASATINIB	ChEMBL	Phase 4 (approved)	RET
ENTRECTINIB	ChEMBL	Phase 4 (approved)	RET
ERLOTINIB	ChEMBL	Phase 4 (approved)	RET
FEDRATINIB	ChEMBL	Phase 4 (approved)	RET
GILTERITINIB	ChEMBL	Phase 4 (approved)	RET
IBRUTINIB	ChEMBL	Phase 4 (approved)	RET
INFIGRATINIB	ChEMBL	Phase 4 (approved)	RET
LAPATINIB	ChEMBL	Phase 4 (approved)	RET
LENVATINIB	ChEMBL	Phase 4 (approved)	RET
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	RET
NILOTINIB	ChEMBL	Phase 4 (approved)	RET
NINTEDANIB	ChEMBL	Phase 4 (approved)	RET
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	RET
PALBOCICLIB	ChEMBL	Phase 4 (approved)	RET
PONATINIB	ChEMBL	Phase 4 (approved)	RET
PRALSETINIB	ChEMBL	Phase 4 (approved)	RET
QUIZARTINIB	ChEMBL	Phase 4 (approved)	RET
RUXOLITINIB	ChEMBL	Phase 4 (approved)	RET
SORAFENIB	ChEMBL	Phase 4 (approved)	RET
SUNITINIB	ChEMBL	Phase 4 (approved)	RET
TIVOZANIB	ChEMBL	Phase 4 (approved)	RET
TOFACITINIB	ChEMBL	Phase 4 (approved)	RET
UPADACITINIB	ChEMBL	Phase 4 (approved)	RET
VANDETANIB	ChEMBL	Phase 4 (approved)	RET
VEMURAFENIB	ChEMBL	Phase 4 (approved)	RET
ALISERTIB	ChEMBL	Phase 3	RET
AMITRIPTYLINOXIDE	ChEMBL	Phase 3	RET
BARASERTIB	ChEMBL	Phase 3	RET
BRIVANIB	ChEMBL	Phase 3	RET
BRIVANIB ALANINATE	ChEMBL	Phase 3	RET
CANERTINIB	ChEMBL	Phase 3	RET
CEDIRANIB	ChEMBL	Phase 3	RET
CRENOLANIB	ChEMBL	Phase 3	RET
DEFACTINIB	ChEMBL	Phase 3	RET
DOVITINIB	ChEMBL	Phase 3	RET
LESTAURTINIB	ChEMBL	Phase 3	RET
LINIFANIB	ChEMBL	Phase 3	RET
MOTESANIB	ChEMBL	Phase 3	RET
ORANTINIB	ChEMBL	Phase 3	RET
POZIOTINIB	ChEMBL	Phase 3	RET
QUERCETIN	ChEMBL	Phase 3	RET
RIVOCERANIB	ChEMBL	Phase 3	RET
SARACATINIB	ChEMBL	Phase 3	RET
SEMAXANIB	ChEMBL	Phase 3	RET
TESEVATINIB	ChEMBL	Phase 3	RET
VATALANIB	ChEMBL	Phase 3	RET
AEE-788	ChEMBL	Phase 2	RET
AT-9283	ChEMBL	Phase 2	RET
AZD-1480	ChEMBL	Phase 2	RET
BAFETINIB	ChEMBL	Phase 2	RET
BEMCENTINIB	ChEMBL	Phase 2	RET
BFH-772	ChEMBL	Phase 2	RET
BMS-690514	ChEMBL	Phase 2	RET
BMS-754807	ChEMBL	Phase 2	RET
BMS-777607	ChEMBL	Phase 2	RET
CENISERTIB	ChEMBL	Phase 2	RET
CEP-11981	ChEMBL	Phase 2	RET
CEP-32496	ChEMBL	Phase 2	RET
CERDULATINIB	ChEMBL	Phase 2	RET
DANUSERTIB	ChEMBL	Phase 2	RET
DEFOSBARASERTIB	ChEMBL	Phase 2	RET
DORAMAPIMOD	ChEMBL	Phase 2	RET
ENMD-2076	ChEMBL	Phase 2	RET
FGFR INHIBITOR DEBIO 1347	ChEMBL	Phase 2	RET
FORETINIB	ChEMBL	Phase 2	RET
GOLVATINIB	ChEMBL	Phase 2	RET
ILORASERTIB	ChEMBL	Phase 2	RET
LUCITANIB	ChEMBL	Phase 2	RET
MERESTINIB	ChEMBL	Phase 2	RET
MILCICLIB	ChEMBL	Phase 2	RET
MIVAVOTINIB	ChEMBL	Phase 2	RET
MK-2461	ChEMBL	Phase 2	RET
NARAZACICLIB	ChEMBL	Phase 2	RET
OSI-027	ChEMBL	Phase 2	RET
OSI-632	ChEMBL	Phase 2	RET
PEXMETINIB	ChEMBL	Phase 2	RET
R-406	ChEMBL	Phase 2	RET
RAF-265	ChEMBL	Phase 2	RET
REBASTINIB	ChEMBL	Phase 2	RET
SAPITINIB	ChEMBL	Phase 2	RET
SCH-900776	ChEMBL	Phase 2	RET
SU-014813	ChEMBL	Phase 2	RET
TG100-801	ChEMBL	Phase 2	RET
TOZASERTIB	ChEMBL	Phase 2	RET