NPASS Compound

Natural Product: NPC485109

Natural Product ID	NPC485109
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	DKOOBSCWJFTXKX-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5487269
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002901] Isoflav-2-enes [CHEMONTID:0000494] Isoflavones

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 57 59 0 0 0 0 0 0 0 0999 V2000 0.4236 5.3315 -1.8732 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1633 4.3087 -1.4730 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0156 3.6512 -0.1377 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1770 4.1419 0.6981 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2355 4.1817 0.5153 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9456 2.1996 -0.2364 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1682 1.5403 0.2217 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3311 0.1783 0.1734 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5408 -0.4831 0.6774 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6615 -0.9213 1.9791 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7507 -1.5105 2.4051 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8049 -1.7371 1.6606 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9345 -2.3725 2.1830 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0022 -2.5784 1.3490 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9775 -2.1762 0.0316 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8646 -1.5489 -0.4872 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7639 -1.3290 0.3461 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6267 -0.7005 -0.1428 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5934 -0.3266 -1.3532 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7818 -1.1212 -1.8071 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1389 -3.2163 1.8693 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7158 -0.5656 -0.3816 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8512 0.0360 -0.8551 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9120 -0.8189 -1.4255 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7009 -1.5446 -0.4482 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8514 -2.8435 -0.4836 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6771 -3.5804 0.5478 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2560 -3.6907 -1.5350 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9516 1.4099 -0.7766 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0902 1.9984 -1.2528 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5045 -1.9520 -0.4095 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3512 5.7941 -1.2925 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5989 5.7446 -2.8553 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9302 3.8907 -2.1132 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9418 5.1906 0.9881 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1194 4.1966 0.1083 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2892 3.5704 1.6300 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2501 3.7444 1.5536 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1651 5.2991 0.6655 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1580 4.0017 -0.0321 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0109 2.1020 0.6629 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8124 -0.7545 2.6321 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9031 -2.6686 3.2236 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8071 -2.3291 -0.6416 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2691 -1.6742 -2.4847 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6453 -3.9060 1.3288 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6063 -0.1100 -1.9719 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4481 -1.4235 -2.2228 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1900 -0.9956 0.3471 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4890 -2.9343 0.9394 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0377 -3.9611 1.3708 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1648 -4.4686 0.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9303 -3.6203 -2.4184 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1803 -4.7573 -1.2255 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2507 -3.3914 -1.8682 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0081 1.9078 -0.8739 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1279 -2.4078 0.4225 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 3 5 1 0 3 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 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 16 20 1 0 14 21 1 0 8 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 3 26 27 1 0 26 28 1 0 23 29 2 0 29 30 1 0 22 31 1 0 29 6 1 0 18 9 1 0 17 12 1 0 1 32 1 0 1 33 1 0 2 34 1 0 4 35 1 0 4 36 1 0 4 37 1 0 5 38 1 0 5 39 1 0 5 40 1 0 7 41 1 0 10 42 1 0 13 43 1 0 15 44 1 0 20 45 1 0 21 46 1 0 24 47 1 0 24 48 1 0 25 49 1 0 27 50 1 0 27 51 1 0 27 52 1 0 28 53 1 0 28 54 1 0 28 55 1 0 30 56 1 0 31 57 1 0 M END

Standard InCHIKey	DKOOBSCWJFTXKX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H26O6/c1-6-25(4,5)18-11-16(22(28)15(23(18)29)8-7-13(2)3)17-12-31-20-10-14(26)9-19(27)21(20)24(17)30/h6-7,9-12,26-29H,1,8H2,2-5H3
SMILES	C=CC(C)(C)c1cc(c2coc3cc(cc(c3c2=O)O)O)c(c(CC=C(C)C)c1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.17	Volume:	441.663 ? Van der Waals volume.
Dense:	0.956	LogP:	4.01 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.167 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.56 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.418	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.343	Fsp³:	0.24
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:	0.978	Fluc inhibitor:	0.289 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.719 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.539 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.476	Promiscuous compounds:	0.072

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.22	MDCK Permeability:	-4.865
Pgp-inhibitor:	0.373	Pgp-substrate:	0.003
PAMPA:	0.234 ? 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):	0.02
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.826
Plasma Protein Binding (PPB):	95.691%	Volume Distribution (VD):	0.241
Fu:	4.569% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.997
BSEP inhibitor:	0.859

ADMET: Metabolism

CYP1A2-inhibitor:	0.538	CYP1A2-substrate:	0.998
CYP2C19-inhibitor:	0.04	CYP2C19-substrate:	0.972
CYP2C9-inhibitor:	0.983	CYP2C9-substrate:	0.133
CYP2D6-inhibitor:	0.962	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

0.861

Half-life (T1/2):

1.699

ADMET: Toxicity

hERG Blockers:	0.049	hERG Blockers (10um):	0.591
Human Hepatotoxicity (H-HT):	0.416	Drug-induced Liver Injury (DILI):	0.815
AMES Toxicity:	0.448	Rat Oral Acute Toxicity:	0.88
Maximum Recommended Daily Dose:	0.955	Skin Sensitization:	0.752
Carcinogencity:	0.52	Eye Corrosion:	0.0
Eye Irritation:	0.95	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.188	Ototoxicity:	0.354
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.212
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.115
A549 Cytotoxicity:	0.775	Hek293 Cytotoxicity:	0.853
BCF:	1.938 ? 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:	4.691 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.217 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.691 ? 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
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26469557]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2681536]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
Inhibition	12

Activity Type	# Activity
Organism	12

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	93.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	17.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	78.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	89.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	70.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	27.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	3.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	0.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	94.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	86.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	81.0	%	PMID[2681536]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	Inhibition	=	63.0	%	PMID[2681536]

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 NPC485109 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	27174
0.1-0.2	20395
0.2-0.3	1843
0.3-0.4	339
0.4-0.5	83
0.5-0.6	18
0.6-0.7	3
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	Natural Product ID
0.7121	Intermediate Similarity	NPC232947
0.6769	Remote Similarity	NPC476055
0.6232	Remote Similarity	NPC238279
0.6087	Remote Similarity	NPC93552
0.5915	Remote Similarity	NPC213659
0.5915	Remote Similarity	NPC85131
0.5915	Remote Similarity	NPC326109
0.589	Remote Similarity	NPC128774
0.5753	Remote Similarity	NPC233918
0.5753	Remote Similarity	NPC268059
0.5694	Remote Similarity	NPC268204
0.5538	Remote Similarity	NPC87545
0.5417	Remote Similarity	NPC55832
0.5309	Remote Similarity	NPC303174
0.5278	Remote Similarity	NPC259166
0.5231	Remote Similarity	NPC39426
0.5135	Remote Similarity	NPC161124
0.5132	Remote Similarity	NPC475705
0.5128	Remote Similarity	NPC231763
0.5077	Remote Similarity	NPC193792
0.507	Remote Similarity	NPC309154
0.5067	Remote Similarity	NPC92075

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485109 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5113
0.1-0.2	4020
0.2-0.3	14
0.3-0.4	2
0.4-0.5	0
0.5-0.6	1
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
0.5231	Remote Similarity	NPD1510	Phase 2

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