NPASS Compound

Natural Product: NPC233502

Natural Product ID	NPC233502
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OHVOXMFXCZKNPR-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5459223
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0001612] Isoflavans [CHEMONTID:0001827] Isoflavanones [CHEMONTID:0003526] 6-prenylated isoflavanones

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 54 57 0 0 0 0 0 0 0 0999 V2000 -8.8295 -0.3928 -0.4434 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8204 0.5754 -0.9407 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7282 0.7831 -0.2135 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5064 0.0686 1.0735 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3932 -0.7129 1.1569 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0592 -0.4714 1.0936 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1472 -1.5410 1.1990 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7947 -1.3136 1.1389 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3102 -0.0398 0.9753 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2065 0.9960 0.8739 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5762 0.8034 0.9305 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1101 0.2169 0.9097 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6740 1.2584 1.6141 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9405 1.5086 1.5722 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7989 0.7987 0.8602 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1378 1.1240 0.8632 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0333 0.3631 0.1045 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5400 -0.7012 -0.6308 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5211 -1.4533 -1.3984 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7977 -1.1401 -1.3932 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3194 -0.0196 -0.6195 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9324 0.9454 -1.6426 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4076 -0.4713 0.3584 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3598 0.6623 0.0895 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1943 -0.9926 -0.6061 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2884 -0.2569 0.1348 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9443 -0.5683 0.1436 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5101 -1.5376 -0.5288 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7235 -2.0476 -1.3384 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0011 1.3067 -2.2138 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2319 0.0016 0.5252 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4374 -1.4132 -0.3516 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.6974 -0.4056 -1.1359 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0084 1.4856 -0.5864 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4049 -0.5644 1.2551 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5705 0.8645 1.8604 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5765 -2.5198 1.3261 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1295 -2.1867 1.2268 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8752 2.0369 0.7417 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2269 1.6880 0.8546 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0387 1.9071 2.2370 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5277 1.9521 1.4341 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1470 -2.2986 -1.9857 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4532 -1.7789 -2.0120 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1885 0.4201 -2.5866 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8338 1.4420 -1.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2006 1.7362 -1.9073 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0979 0.3872 0.4652 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8863 -1.4019 0.0522 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9188 -0.6337 1.3351 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2302 -2.8785 -1.5814 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2560 1.0004 -2.9866 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9734 2.3882 -2.0024 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9952 1.0208 -2.6461 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 2 0 9 10 1 0 10 11 2 0 9 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 1 0 21 24 1 0 18 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 25 29 1 0 2 30 1 0 11 6 1 0 27 12 1 0 26 15 1 0 24 17 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 7 37 1 0 8 38 1 0 10 39 1 0 11 40 1 0 13 41 1 0 16 42 1 0 19 43 1 0 20 44 1 0 22 45 1 0 22 46 1 0 22 47 1 0 23 48 1 0 23 49 1 0 23 50 1 0 29 51 1 0 30 52 1 0 30 53 1 0 30 54 1 0 M END

Standard InCHIKey	OHVOXMFXCZKNPR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C25H24O5/c1-15(2)10-12-28-17-7-5-16(6-8-17)19-14-29-21-13-20-18(9-11-25(3,4)30-20)23(26)22(21)24(19)27/h5-11,13-14,26H,12H2,1-4H3
SMILES	CC(=CCOc1ccc(cc1)c1coc2cc3c(C=CC(C)(C)O3)c(c2c1=O)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.16	Volume:	424.317 ? Van der Waals volume.
Dense:	0.952	LogP:	5.148 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.816 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.953 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	68.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.565	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.962	Fsp³:	0.24
MCE-18:	51.613 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.978	Fluc inhibitor:	0.832 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.818 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.819 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.23	Promiscuous compounds:	0.202

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.001	MDCK Permeability:	-4.646
Pgp-inhibitor:	0.932	Pgp-substrate:	0.009
PAMPA:	0.674 ? 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):	0.035
20% Bioavailability (F20%):	0.639	30% Bioavailability (F30%):	0.929
50% Bioavailability (F50%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.219	MRP1:	0.931
Plasma Protein Binding (PPB):	97.902%	Volume Distribution (VD):	0.007
Fu:	1.868% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.992
OATP1B3 inhibitor:	0.937	BCRP inhibitor:	0.933
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.995	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.557	CYP2C19-substrate:	0.919
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.947
CYP2D6-inhibitor:	0.769	CYP2D6-substrate:	0.166
CYP3A4-inhibitor:	0.007	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.013	CYP2C8-inhibitor:	1.0
HLM stability:	0.85 ? 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):

5.739

Half-life (T1/2):

0.667

ADMET: Toxicity

hERG Blockers:	0.323	hERG Blockers (10um):	0.621
Human Hepatotoxicity (H-HT):	0.61	Drug-induced Liver Injury (DILI):	0.89
AMES Toxicity:	0.644	Rat Oral Acute Toxicity:	0.525
Maximum Recommended Daily Dose:	0.623	Skin Sensitization:	0.482
Carcinogencity:	0.805	Eye Corrosion:	0.0
Eye Irritation:	0.596	Respiratory Toxicity:	0.826
Drug-induced Neurotoxicity:	0.333	Ototoxicity:	0.471
Hematotoxicity:	0.314	Drug-induced Nephrotoxicity:	0.517
Genotoxicity:	0.471	RPMI-8226 Immunitoxicity:	0.121
A549 Cytotoxicity:	0.198	Hek293 Cytotoxicity:	0.389
BCF:	2.088 ? 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:	4.902 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.768 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.252 ? 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
NPO40204	Millettia extensa	Species	Fabaceae	Eukaryota	Stems	n.a.	n.a.	PMID[30106294]
NPO40204	Millettia extensa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31403786]

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
MIC	2

Activity Type	# Activity
Organism	2

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	MIC	=	128.0	ug.mL-1	PMID[30106294]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	=	128.0	ug.mL-1	PMID[30106294]

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 NPC233502 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	22774
0.1-0.2	24129
0.2-0.3	2428
0.3-0.4	385
0.4-0.5	100
0.5-0.6	21
0.6-0.7	11
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC113475
0.75	Intermediate Similarity	NPC97716
0.7273	Intermediate Similarity	NPC484041
0.726	Intermediate Similarity	NPC184755
0.6974	Remote Similarity	NPC604503
0.6842	Remote Similarity	NPC229847
0.6711	Remote Similarity	NPC484043
0.662	Remote Similarity	NPC203636
0.6533	Remote Similarity	NPC84124
0.6533	Remote Similarity	NPC184547
0.6438	Remote Similarity	NPC249824
0.64	Remote Similarity	NPC608710
0.6216	Remote Similarity	NPC133400
0.6071	Remote Similarity	NPC484047
0.6071	Remote Similarity	NPC484042
0.5904	Remote Similarity	NPC302762
0.5854	Remote Similarity	NPC238064
0.5854	Remote Similarity	NPC189270
0.5854	Remote Similarity	NPC5840
0.5694	Remote Similarity	NPC473076
0.557	Remote Similarity	NPC488570
0.55	Remote Similarity	NPC231763
0.55	Remote Similarity	NPC107838
0.5467	Remote Similarity	NPC254741
0.5455	Remote Similarity	NPC488135
0.5385	Remote Similarity	NPC219917
0.5385	Remote Similarity	NPC40942
0.5309	Remote Similarity	NPC237635
0.5256	Remote Similarity	NPC166054
0.5244	Remote Similarity	NPC178964
0.5185	Remote Similarity	NPC474052
0.5181	Remote Similarity	NPC170026
0.5062	Remote Similarity	NPC6511
0.5062	Remote Similarity	NPC479305
0.506	Remote Similarity	NPC229632
0.5057	Remote Similarity	NPC278968

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC233502 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3738
0.1-0.2	5308
0.2-0.3	100
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