NPASS Compound

Natural Product: NPC472029

Natural Product ID	NPC472029
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	YMYBAWFGDGMZLY-GXDHUFHOSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3331100
PubChem CID	n.a.
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 55 55 0 0 0 0 0 0 0 0999 V2000 -6.4722 2.2718 0.0913 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1195 2.3469 -0.5364 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4563 0.9985 -0.5337 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2535 -0.0270 -1.2984 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0413 1.0853 -0.9582 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5406 2.2128 -1.2539 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2571 -0.1345 -1.0240 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2192 -0.8424 -2.1998 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4813 -2.0256 -2.3050 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7764 -2.4987 -1.2172 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8189 -1.7788 -0.0329 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0668 -2.2893 1.1161 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3800 -2.0053 0.9133 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0852 -1.2659 1.7436 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4242 -0.6710 2.9566 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5213 -1.0100 1.5022 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8456 0.4538 1.3489 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3015 0.5834 1.1136 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7810 1.1404 -0.0004 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2506 1.2704 -0.2361 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8119 1.6346 -1.0134 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5574 -0.5946 0.0726 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5936 0.1149 1.2556 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0410 -3.6737 -1.3143 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9333 -0.3488 -3.2792 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7403 1.3047 0.5108 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6042 3.0258 0.9160 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2693 2.5344 -0.6632 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1487 2.7955 -1.5617 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4992 3.0326 0.0737 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4220 0.6889 0.5537 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2856 -0.1420 -0.8568 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4327 0.2725 -2.3447 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7192 -0.9911 -1.3081 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4717 -2.5602 -3.2451 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4372 -1.8595 2.0686 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1562 -3.4073 1.1781 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8405 -2.4424 0.0329 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2066 -0.2243 3.6216 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9120 -1.4348 3.5510 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7899 0.1594 2.6263 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8539 -1.5272 0.5900 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0725 -1.3697 2.4077 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2591 0.9389 0.5509 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5890 1.0227 2.2894 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9881 0.2184 1.8610 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6968 0.3216 -0.5499 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6863 1.6607 0.7120 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3973 2.0305 -1.0210 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2119 2.4906 -0.6025 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3728 2.0158 -1.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0874 0.8274 -1.3101 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7657 1.1054 1.2790 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0844 -4.3968 -0.6043 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7005 0.4856 -3.7840 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 2 3 19 20 1 0 19 21 1 0 11 22 2 0 22 23 1 0 10 24 1 0 8 25 1 0 22 7 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 0 2 30 1 0 3 31 1 0 4 32 1 0 4 33 1 0 4 34 1 0 9 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 15 39 1 0 15 40 1 0 15 41 1 0 16 42 1 0 16 43 1 0 17 44 1 0 17 45 1 0 18 46 1 0 20 47 1 0 20 48 1 0 20 49 1 0 21 50 1 0 21 51 1 0 21 52 1 0 23 53 1 0 24 54 1 0 25 55 1 0 M END

Standard InCHIKey	YMYBAWFGDGMZLY-GXDHUFHOSA-N
Standard InCHI	InChI=1S/C21H30O4/c1-6-15(5)20(24)19-18(23)12-17(22)16(21(19)25)11-10-14(4)9-7-8-13(2)3/h8,10,12,15,22-23,25H,6-7,9,11H2,1-5H3/b14-10+
SMILES	CCC(C)C(=O)c1c(cc(c(C/C=C(C)/CCC=C(C)C)c1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.21	Volume:	382.558 ? Van der Waals volume.
Dense:	0.905	LogP:	5.689 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.015 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.188 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	9.0
TPSA:	77.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.443	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.42	Fsp³:	0.476
MCE-18:	24.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.726	Fluc inhibitor:	0.036 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.528 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.276 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.708	Promiscuous compounds:	0.231

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.933	MDCK Permeability:	-4.672
Pgp-inhibitor:	0.993	Pgp-substrate:	0.003
PAMPA:	0.017 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.033	30% Bioavailability (F30%):	0.448
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.988
Plasma Protein Binding (PPB):	96.535%	Volume Distribution (VD):	0.159
Fu:	3.351% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.955
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.571
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.999
CYP2C9-inhibitor:	0.926	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.38
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

7.048

Half-life (T1/2):

0.801

ADMET: Toxicity

hERG Blockers:	0.058	hERG Blockers (10um):	0.613
Human Hepatotoxicity (H-HT):	0.703	Drug-induced Liver Injury (DILI):	0.395
AMES Toxicity:	0.147	Rat Oral Acute Toxicity:	0.372
Maximum Recommended Daily Dose:	0.357	Skin Sensitization:	0.971
Carcinogencity:	0.235	Eye Corrosion:	0.003
Eye Irritation:	0.865	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.298	Ototoxicity:	0.453
Hematotoxicity:	0.362	Drug-induced Nephrotoxicity:	0.54
Genotoxicity:	0.215	RPMI-8226 Immunitoxicity:	0.195
A549 Cytotoxicity:	0.589	Hek293 Cytotoxicity:	0.479
BCF:	2.167 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	4.996 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.548 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.092 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO30921	Hypericum roeperianum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24930002]
NPO30921	Hypericum roeperianum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26358281]
NPO40851	Garcinia dauphinensis	Species	Clusiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30354100]
NPO30921	Hypericum roeperianum	Species	Hypericaceae	Eukaryota	n.a.	root	n.a.	PMID[8862040]
NPO40851	Garcinia dauphinensis	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30921	Hypericum roeperianum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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	4
EC50	1
MIC	3
GI	3
Activity	1
CC50	1

Activity Type	# Activity
Individual protein	2
Cell line	5
Organism	5
Non-molecular	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT324	Individual protein	Cyclooxygenase-1	Ovis aries	IC50	=	5800000.0	nM	PMID[31255927]
NPT3068	Individual protein	Leukotriene B4 receptor 1	Homo sapiens	IC50	=	26200000.0	nM	PMID[31255927]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT306	Cell line	PC-3	Homo sapiens	GI	=	20.0	%	PMID[1791472]
NPT306	Cell line	PC-3	Homo sapiens	GI	<	20.0	%	PMID[1791472]
NPT139	Cell line	HT-29	Homo sapiens	GI	=	20.0	%	PMID[17067155]
NPT179	Cell line	A2780	Homo sapiens	IC50	=	12400.0	nM	PMID[30354100]
NPT25	Cell line	MT4	Homo sapiens	CC50	=	26700.0	nM	PMID[23013292]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	11000.0	nM	PMID[25128665]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	>	26700.0	nM	PMID[22672802]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	1.0	ug.mL-1	PMID[18183025]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	1.0	ug.mL-1	PMID[26046820]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	>	1.0	ug.mL-1	Open TG-GATES in vivo data: Biochemistry
NPT530	Organism	Caenorhabditis elegans	Caenorhabditis elegans	Activity	=	37.0	%	PMID[18077363]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

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 NPC472029 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	11195
0.1-0.2	34827
0.2-0.3	3305
0.3-0.4	389
0.4-0.5	116
0.5-0.6	20
0.6-0.7	4
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
0.8913	High Similarity	NPC65761
0.8444	Intermediate Similarity	NPC91105
0.6842	Remote Similarity	NPC23126
0.6667	Remote Similarity	NPC483966
0.6296	Remote Similarity	NPC478710
0.6087	Remote Similarity	NPC215392
0.5862	Remote Similarity	NPC105157
0.5667	Remote Similarity	NPC602136
0.5636	Remote Similarity	NPC606098
0.5593	Remote Similarity	NPC478708
0.5536	Remote Similarity	NPC475733
0.55	Remote Similarity	NPC478709
0.541	Remote Similarity	NPC478706
0.5362	Remote Similarity	NPC482843
0.5323	Remote Similarity	NPC266689
0.5286	Remote Similarity	NPC482841
0.5273	Remote Similarity	NPC263753
0.5246	Remote Similarity	NPC478707
0.5172	Remote Similarity	NPC98254
0.5156	Remote Similarity	NPC264112
0.5147	Remote Similarity	NPC290133
0.5094	Remote Similarity	NPC12640
0.5091	Remote Similarity	NPC201662
0.5079	Remote Similarity	NPC267846
0.5075	Remote Similarity	NPC477242
0.507	Remote Similarity	NPC483013

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC472029 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3361
0.1-0.2	5717
0.2-0.3	69
0.3-0.4	3
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