Table 3 Exploration of proteins modified by weight loss interventions and in a Mendelian randomisation framework as therapeutic targets.

Gene	Target	Protein full name	Direction of relationship with BMI	Current or potential to be small-molecule target¹	Current or potential to be biologic target¹	Protein involved in ADME¹	Tier¹	Drug which involves protein target and therapeutic use (approved only)²
IGFBP1	IGFBP1	Insulin-like growth factor binding protein 1	Lower BMI increases protein	Y	Y	N	2	Mecasermin: IGFBP1 is a carrier for this recombinant IGF1. Used in growth failure as a result of insulin-like growth factor 1 deficiency in paediatric patients
ADH4	ADH4	Alcohol dehydrogenase 4	Lower BMI reduces protein	Y	N	Y	1	Ethanol: chronic pain NADH: nutritional supplement
RTN4R	Nogo Receptor	Reticulon-4 receptor	Lower BMI reduces protein	Y	Y	N	3A	NA
IL1RN	IL-1Ra	Interleukin-1 receptor antagonist protein	Lower BMI reduces protein	N	Y	N	3A	NA
IGFBP2	IGFBP2	Insulin-like growth factor binding protein-2	Lower BMI increases protein	Y	Y	N	2	Mecasermin: IGFBP2 is a carrier for this recombinant IGF1. Used in growth failure as a result of insulin-like growth factor 1 deficiency in paediatric patients
BCAN	PGCB	Brevican core protein	Lower BMI increases protein	N	Y	N	3B	NA

¹Information from Supplementary Table 1 in Finan et al.³⁴ Y = yes, N = no. Small molecule = chemically derived, biologic = extracted from living organism. ²Information from DrugBank³³. ADME = absorption, digestion, metabolism, excretion³⁴. Tier 1 = target with approved small molecule or biologics, or drug candidate in clinical phase. Tier 2 = target with known bioactive drug-like small molecular binding partners or have high similarity to approved drug targets. Tier 3 = structural similarities to approved drugs (to a lesser degree than Tier 2) or are a protein with known potential to be targeted (such as a G protein-coupled receptor)³⁴. More details can be found by Finan et al.

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