Alectinib Comprehensive Drug Mechanism & Clinical Trial Analysis

Comprehensive Alectinib Mechanism Analysis

1. UniProt Protein Targets (33 Total) Primary Targets (IC50 < 10 nM)

UniProt ID	Protein Name	Type	IC50
Q9UM73	ALK tyrosine kinase receptor	Primary	0.59-1.9 nM
P07949	RET proto-oncogene kinase	Primary	~2 nM
P08922	ROS1 proto-oncogene kinase	Primary	~3 nM

Secondary/Off-Targets (IC50 10-100 nM)

UniProt ID	Protein Name	Type
P00533	Epidermal growth factor receptor (EGFR)	Off-target kinase
P35968	VEGFR2	Off-target kinase
P16591	Tyrosine-protein kinase Fer	Off-target kinase
P21709	Ephrin type-A receptor 1	Off-target kinase

Low-Affinity Off-Targets (IC50 > 100 nM)

UniProt ID	Protein Name	Type
P49759, P49760, P49761	CLK1/2/3 kinases	Splicing kinases
O14976	Cyclin-G-associated kinase	Cell cycle
Q96SB4, P78362	SRPK1/2	SR protein kinases
Q96RR4	CaMKK2	Calcium signaling
P41595	5-HT2B receptor	Serotonin receptor
P21728, P35462	D1A/D3 dopamine receptors	Dopamine receptors
P03372, P06401, P15207	Estrogen/Progesterone/Androgen receptors	Nuclear receptors
P23975, P31645	NET/SERT transporters	Neurotransmitter transporters
Q9UNQ0, O95342	ABCG2/BSEP	ABC transporters
Q14432, P27815	PDE3A/PDE4A	Phosphodiesterases
P15735	Phosphorylase kinase gamma	Metabolic enzyme
P78368	CK1 gamma-2	Casein kinase
P0DMS8	Adenosine A3 receptor	GPCR
O75469	PXR (NR1I2)	Nuclear receptor
Q9HC35	EML4	Microtubule protein
Q15067, O15254	ACOX1/ACOX3	Peroxisomal enzymes

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2. Clinical Trials (66 Total) Breakdown by Phase: Phase: Phase 4 Count: 1 Trial IDs: NCT05525338 Phase: Phase 3 Count: 8 Trial IDs: NCT02075840, NCT02604342, NCT02838420, NCT03596866, NCT03768063, NCT05170204, NCT06624059, NCT06765109 Phase: Phase 2/3 Count: 3 Trial IDs: NCT03178552, NCT05722886, NCT05770037 Phase: Phase 2 Count: 20 Trial IDs: NCT02091141, NCT02314481, NCT02925234, NCT03155009, NCT03445000, NCT03498521, NCT03737994, NCT03779191, NCT03944772, NCT04116541, NCT04302025, NCT04322890, NCT04341181, NCT04423185, NCT04551521, NCT04589845, NCT04591431, NCT04632992, NCT04644315, NCT05015010, NCT05081674, NCT05159245, NCT05725200 Phase: Phase 1/2 Count: 10 Trial IDs: NCT01801111, NCT01871805, NCT02521051, NCT03131206, NCT03158389, NCT03202940, NCT04774718, NCT05713006, NCT05987644, NCT06691491 Phase: Phase 1 Count: 6 Trial IDs: NCT01940510, NCT01981005, NCT01984229, NCT02013219, NCT02023125, NCT02621047, NCT07001384 Phase: Early Phase 1 Count: 1 Trial IDs: NCT05238831 (withdrawn) Phase: Observational Count: 12 Trial IDs: NCT03271554, NCT03546894, NCT04351334, NCT04647110, NCT04708639, NCT04764188, NCT05525858, NCT05834348, NCT06532149, NCT06709274, NCT06862869 Phase: Expanded Access Count: 1 Trial IDs: NCT02271139

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3. Disease Indications Approved (Phase 4):

• Non-Small Cell Lung Cancer (NSCLC) - ALK-positive (primary indication)

• Neoplasms (general oncology) Phase 3 Investigation:

• Carcinoma, Non-Small-Cell Lung (additional settings) Phase 2 Investigation:

Disease	MeSH ID
Anaplastic Large Cell Lymphoma	D017728
Thyroid Neoplasms	D013964
Melanoma	D008545
Sarcoma	D012509
Brain Tumors (glioblastoma)	D001932
Colorectal Neoplasms	D015179
Head and Neck Neoplasms	D006258
Ovarian Neoplasms	D010051
Pancreatic Neoplasms	D010190
Cholangiocarcinoma	D018281
Neuroendocrine Tumors	D018358
Bronchial Neoplasms	D001984
Salivary Gland Neoplasms	D012468
Hematologic Neoplasms	D019337

Phase 1 Investigation:

• Glioblastoma, Glioma
• Hepatocellular Carcinoma
• Liver Diseases

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4. Activity Records ChEMBL: 96 Activity Records Highly Potent (IC50 < 5 nM):

Activity ID	Type	Value	Target
CHEMBL_ACT_22775265	IC50	0.59 nM	ALK
CHEMBL_ACT_22775391	IC50	0.96 nM	ALK
CHEMBL_ACT_22775387	IC50	1.5 nM	ALK
CHEMBL_ACT_24867175	IC50	1.56 nM	ALK
CHEMBL_ACT_19036772	IC50	1.9 nM	ALK
CHEMBL_ACT_16426638	IC50	2.0 nM	ALK
CHEMBL_ACT_22775383	IC50	3.9 nM	RET/ROS

Kd Values (Binding Affinity):

Activity ID	Type	Value
CHEMBL_ACT_17899274	Kd	193 nM
CHEMBL_ACT_17904277	Kd	259 nM
CHEMBL_ACT_17879571	Kd	271 nM
CHEMBL_ACT_17935142	Kd	369 nM
CHEMBL_ACT_17894491	Kd	514 nM

PubChem	- PubChem CID	- FDA Approved
24 Bioactivity Records
	49806720	Yes

- 555 PubMed literature references - 4,831 patent references

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5. Molecules Sharing Alectinib Targets ALK Inhibitors (32 molecules, Phase 3+):

Molecule	Status	Notes
Crizotinib	Approved	1st-gen ALK inhibitor
Ceritinib	Approved	2nd-gen ALK inhibitor
Brigatinib	Approved	2nd-gen ALK inhibitor
Lorlatinib	Approved	3rd-gen ALK inhibitor
Entrectinib	Approved	ALK/ROS1/NTRK
Repotrectinib	Approved	Next-gen ALK/ROS1
Gilteritinib	Approved	FLT3/ALK

RET Inhibitors (66 molecules, Phase 3+):

Molecule	Status	Specificity
Selpercatinib	Approved	RET-selective
Pralsetinib	Approved	RET-selective
Cabozantinib	Approved	Multi-kinase
Vandetanib	Approved	Multi-kinase
Lenvatinib	Approved	Multi-kinase

ROS1 Inhibitors (20 molecules, Phase 3+):

Molecule	Status
Crizotinib	Approved (ROS1 indication)
Entrectinib	Approved (ROS1 indication)
Lorlatinib	Approved
Repotrectinib	Approved

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Summary

Metric	Value
Total UniProt Targets	33
Primary Targets	3 (ALK, RET, ROS1)
Off-Targets	30
Clinical Trials	66
ChEMBL Activity Records	96
PubChem Bioactivity Records	24
Approved Indication	ALK+ NSCLC
Competing ALK Inhibitors (Phase 3+)	32 molecules
Most Potent IC50	0.59 nM (ALK)