NPASS Compound

Natural Product: NPC91105

Natural Product ID	NPC91105
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2,4,6-Trihydroxy-3-Geranylacetophenone
IUPAC Name	1-[3-[(2E)-3,7-dimethylocta-2,6-dienyl]-2,4,6-trihydroxyphenyl]ethanone
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1242095
PubChem CID	11808877
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003670] Aryl ketones [CHEMONTID:0004296] Phenylketones [CHEMONTID:0004298] Alkyl-phenylketones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 46 46 0 0 0 0 0 0 0 0999 V2000 4.5598 2.2442 1.3547 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4931 0.8155 0.9167 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6498 0.3884 0.0085 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6246 -1.0387 -0.3904 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2795 -1.6771 -0.1250 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2041 -0.9516 -0.9040 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2234 -0.3972 -0.2154 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8595 0.3227 -0.8835 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2183 -0.1700 -0.6012 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7862 -1.3062 -1.1257 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0842 -1.6808 -0.7940 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8335 -0.9167 0.0723 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2889 0.2484 0.6276 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0849 1.0470 1.5395 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2441 0.6878 1.8193 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5401 2.2782 2.1393 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9994 0.5791 0.2698 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4717 1.7428 0.8318 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1288 -1.2528 0.4286 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0278 -2.0714 -1.9972 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2610 -0.8570 -2.3810 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4299 -0.1520 1.5488 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4174 2.4074 2.0367 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6526 2.5869 1.8515 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7521 2.8703 0.4633 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9485 1.1049 -0.4661 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3615 -1.5830 0.2310 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9511 -1.1935 -1.4477 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0915 -1.6039 0.9578 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3074 -2.7191 -0.4806 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2064 -0.4688 0.8682 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7301 0.2330 -2.0003 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7904 1.4053 -0.6486 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4989 -2.5647 -1.2136 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3111 3.0687 1.3753 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3146 2.7626 2.8004 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6852 2.0690 2.8044 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7042 1.7395 1.4898 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3275 -1.7262 1.3079 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4673 -2.8105 -1.5917 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3894 -1.2373 -2.9101 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2152 -1.2566 -2.7828 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3021 0.2493 -2.6130 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1113 0.3568 2.2588 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0832 -0.6187 0.7751 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8818 -0.9540 2.1011 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 13 17 2 0 17 18 1 0 12 19 1 0 10 20 1 0 6 21 1 0 2 22 1 0 17 9 1 0 1 23 1 0 1 24 1 0 1 25 1 0 3 26 1 0 4 27 1 0 4 28 1 0 5 29 1 0 5 30 1 0 7 31 1 0 8 32 1 0 8 33 1 0 11 34 1 0 16 35 1 0 16 36 1 0 16 37 1 0 18 38 1 0 19 39 1 0 20 40 1 0 21 41 1 0 21 42 1 0 21 43 1 0 22 44 1 0 22 45 1 0 22 46 1 0 M END

Standard InCHIKey	RCOXTTLIGHDQHU-XYOKQWHBSA-N
Standard InCHI	InChI=1S/C18H24O4/c1-11(2)6-5-7-12(3)8-9-14-15(20)10-16(21)17(13(4)19)18(14)22/h6,8,10,20-22H,5,7,9H2,1-4H3/b12-8+
SMILES	CC(=CCC/C(=C/Cc1c(cc(c(C(=O)C)c1O)O)O)/C)C

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO16744	Melicope ptelefolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21958738]
NPO16744	Melicope ptelefolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16744	Melicope ptelefolia	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	15
Inhibition	12
Activity	6

Activity Type	# Activity
Individual protein	20
Cell line	4
Others	2
Organism	6
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	IC50	=	6900.0	nM	PMID[573799]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	IC50	=	400.0	nM	PMID[97381]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	Inhibition	=	60.0	%	PMID[97381]
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	Inhibition	=	91.0	%	PMID[97381]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	Inhibition	=	100.0	%	PMID[97381]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	Inhibition	=	28.0	%	PMID[10780913]
NPT31	Individual protein	Cyclooxygenase-2	Homo sapiens	Inhibition	=	14.0	%	PMID[10780913]
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	Inhibition	=	-9.0	%	PMID[6688830]
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	Inhibition	=	-1.0	%	PMID[10780913]
NPT30	Individual protein	Cyclooxygenase-1	Homo sapiens	Inhibition	=	-5.0	%	PMID[6688830]
NPT3806	Individual protein	Arachidonate 5-lipoxygenase	Mus musculus	IC50	=	1800.0	nM	PMID[8277308]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	IC50	=	420.0	nM	PubChem BioAssay data set
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	75.0	%	PMID[573799]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	102.0	%	PMID[19836230]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	13.0	%	PMID[97381]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	6.0	%	PMID[97381]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Activity	<	50.0	%	PMID[28240894]
NPT956	Individual protein	Prostaglandin E synthase	Homo sapiens	IC50	=	3500.0	nM	PMID[28240894]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	IC50	=	1400.0	nM	PMID[28240894]
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	IC50	=	1000.0	nM	PMID[28240894]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	21000.0	nM	PMID[16038541]
NPT81	Cell line	A549	Homo sapiens	IC50	=	20000.0	nM	PMID[23819871]
NPT139	Cell line	HT-29	Homo sapiens	IC50	=	19000.0	nM	PMID[11141107]
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	19000.0	nM	PMID[12662097]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	6600.0	nM	PMID[27228055]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	22500.0	nM	PMID[25128665]
NPT1	Others	Radical scavenging activity	n.a.	IC50	=	46000.0	nM	PMID[8277308]
NPT2	Others	Unspecified	n.a.	IC50	=	20390.0	nM	DOI[10.6019/CHEMBL1201861]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	32.0	%	PMID[28240894]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	38.0	%	PMID[28240894]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	5.0	10'6No_unit	PMID[28240894]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	11.3	ng/ml	PMID[28240894]
NPT32	Organism	Mus musculus	Mus musculus	Activity	=	57.3	ng/ml	PMID[28240894]

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC91105 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	13745
0.1-0.2	32021
0.2-0.3	3500
0.3-0.4	421
0.4-0.5	134
0.5-0.6	24
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8636	High Similarity	NPC65761
0.8444	Intermediate Similarity	NPC472029
0.7308	Intermediate Similarity	NPC483966
0.725	Intermediate Similarity	NPC215392
0.717	Intermediate Similarity	NPC23126
0.6415	Remote Similarity	NPC105157
0.62	Remote Similarity	NPC606098
0.6182	Remote Similarity	NPC602136
0.58	Remote Similarity	NPC263753
0.5625	Remote Similarity	NPC12640
0.56	Remote Similarity	NPC201662
0.5577	Remote Similarity	NPC208891
0.5517	Remote Similarity	NPC267846
0.5517	Remote Similarity	NPC266689
0.5385	Remote Similarity	NPC99836
0.537	Remote Similarity	NPC98254
0.537	Remote Similarity	NPC479053
0.5333	Remote Similarity	NPC116513
0.5333	Remote Similarity	NPC264112
0.5312	Remote Similarity	NPC290133
0.5273	Remote Similarity	NPC600345
0.5238	Remote Similarity	NPC477242
0.5185	Remote Similarity	NPC475733
0.5179	Remote Similarity	NPC194579
0.5094	Remote Similarity	NPC102384
0.5091	Remote Similarity	NPC478710
0.5088	Remote Similarity	NPC180261
0.5085	Remote Similarity	NPC37299
0.5085	Remote Similarity	NPC105493
0.5077	Remote Similarity	NPC228504
0.5075	Remote Similarity	NPC58805
0.5075	Remote Similarity	NPC185276

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC91105 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3407
0.1-0.2	5675
0.2-0.3	64
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data