NPASS Compound

Natural Product: NPC328042

Natural Product ID	NPC328042
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	UABMFOBSIHSWFQ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	23724670
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones

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 32 34 0 0 0 0 0 0 0 0999 V2000 -0.1389 0.7280 1.4820 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6138 0.3616 0.0762 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2496 -0.6109 -0.4847 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6066 -0.3178 -0.4778 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4827 -0.9192 -1.3577 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8393 -0.6488 -1.3761 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3438 0.2641 -0.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5086 0.8920 0.4256 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1528 0.6036 0.4236 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2402 1.2440 1.3558 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6109 2.2212 2.0467 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7036 0.5407 -0.4865 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6797 -1.2980 -2.3010 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0184 -0.0434 0.0586 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9766 0.8730 -0.3443 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3172 0.5918 -0.3957 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7652 -0.6578 -0.0341 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8197 -1.5941 0.3740 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4769 -1.2829 0.4158 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0920 -0.9641 -0.0758 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8514 1.5216 1.8338 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2046 -0.1514 2.1508 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4828 1.2779 -0.5341 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1239 -1.6534 -2.0941 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9087 1.6104 1.1345 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2640 0.6238 0.3531 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5388 -1.7154 -1.9191 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6669 1.8789 -0.6409 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0483 1.3214 -0.7131 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1669 -2.5860 0.6619 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7886 -2.0408 0.7379 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8250 -0.3214 0.1790 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 4 5 2 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 7 12 1 0 6 13 1 0 2 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 10 1 1 0 9 4 1 0 19 14 1 0 1 21 1 0 1 22 1 0 2 23 1 0 5 24 1 0 8 25 1 0 12 26 1 0 13 27 1 0 15 28 1 0 16 29 1 0 18 30 1 0 19 31 1 0 20 32 1 0 M END

Standard InCHIKey	UABMFOBSIHSWFQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H12O5/c16-9-3-1-8(2-4-9)14-6-11(17)10-5-12(18)13(19)7-15(10)20-14/h1-5,7,14,16,18-19H,6H2
SMILES	C1C(OC2=CC(=C(C=C2C1=O)O)O)C3=CC=C(C=C3)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	272.07	Volume:	267.823 ? Van der Waals volume.
Dense:	1.016	LogP:	1.978 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.145 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.691 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.694	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.821	Fsp³:	0.133
MCE-18:	55.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.715	Fluc inhibitor:	0.862 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.815 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.31 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.577	Promiscuous compounds:	0.079

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.964	MDCK Permeability:	-4.76
Pgp-inhibitor:	0.086	Pgp-substrate:	0.018
PAMPA:	0.931 ? 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):	0.005
20% Bioavailability (F20%):	0.049	30% Bioavailability (F30%):	0.822
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.851
Plasma Protein Binding (PPB):	90.136%	Volume Distribution (VD):	-0.348
Fu:	11.489% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.821
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.992
BSEP inhibitor:	0.631

ADMET: Metabolism

CYP1A2-inhibitor:	0.03	CYP1A2-substrate:	0.822
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.935
CYP2C9-inhibitor:	0.054	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.129	CYP2D6-substrate:	0.98
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.445
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.701
HLM stability:	0.965 ? 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):

12.053

Half-life (T1/2):

1.826

ADMET: Toxicity

hERG Blockers:	0.198	hERG Blockers (10um):	0.664
Human Hepatotoxicity (H-HT):	0.686	Drug-induced Liver Injury (DILI):	0.483
AMES Toxicity:	0.663	Rat Oral Acute Toxicity:	0.499
Maximum Recommended Daily Dose:	0.654	Skin Sensitization:	0.883
Carcinogencity:	0.606	Eye Corrosion:	0.021
Eye Irritation:	0.986	Respiratory Toxicity:	0.372
Drug-induced Neurotoxicity:	0.25	Ototoxicity:	0.504
Hematotoxicity:	0.128	Drug-induced Nephrotoxicity:	0.25
Genotoxicity:	0.872	RPMI-8226 Immunitoxicity:	0.032
A549 Cytotoxicity:	0.598	Hek293 Cytotoxicity:	0.647
BCF:	1.129 ? 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:	3.761 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.438 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.104 ? 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
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	heartwood	n.a.	n.a.	PMID[23743282]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9525107]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18117	Dalbergia odorifera	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO18117	Dalbergia odorifera	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

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

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 NPC328042 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	25972
0.1-0.2	19463
0.2-0.3	3655
0.3-0.4	570
0.4-0.5	148
0.5-0.6	33
0.6-0.7	8
0.7-0.8	1
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
0.7556	Intermediate Similarity	NPC329225
0.7556	Intermediate Similarity	NPC147686
0.7292	Intermediate Similarity	NPC1612
0.7292	Intermediate Similarity	NPC183959
0.6667	Remote Similarity	NPC210084
0.6531	Remote Similarity	NPC476480
0.6531	Remote Similarity	NPC84585
0.64	Remote Similarity	NPC264083
0.62	Remote Similarity	NPC225153
0.62	Remote Similarity	NPC479876
0.6078	Remote Similarity	NPC32441
0.6078	Remote Similarity	NPC79943
0.5965	Remote Similarity	NPC39329
0.5965	Remote Similarity	NPC51032
0.5849	Remote Similarity	NPC300668
0.5849	Remote Similarity	NPC329203
0.5849	Remote Similarity	NPC324386
0.5849	Remote Similarity	NPC222342
0.5741	Remote Similarity	NPC321011
0.5741	Remote Similarity	NPC294852
0.5741	Remote Similarity	NPC469764
0.5741	Remote Similarity	NPC188679
0.5741	Remote Similarity	NPC606248
0.5577	Remote Similarity	NPC103991
0.5517	Remote Similarity	NPC169591
0.5517	Remote Similarity	NPC298223
0.5517	Remote Similarity	NPC604412
0.5472	Remote Similarity	NPC472460
0.5455	Remote Similarity	NPC475267
0.5455	Remote Similarity	NPC486095
0.5424	Remote Similarity	NPC472580
0.5333	Remote Similarity	NPC221432
0.5333	Remote Similarity	NPC257097
0.5273	Remote Similarity	NPC99597
0.5273	Remote Similarity	NPC610021
0.5254	Remote Similarity	NPC143896
0.5185	Remote Similarity	NPC204515
0.5185	Remote Similarity	NPC603284
0.5094	Remote Similarity	NPC265871
0.5094	Remote Similarity	NPC205093
0.5091	Remote Similarity	NPC167624
0.5091	Remote Similarity	NPC166482
0.5088	Remote Similarity	NPC474208
0.5079	Remote Similarity	NPC474033
0.5077	Remote Similarity	NPC248593

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC328042 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4560
0.1-0.2	4417
0.2-0.3	163
0.3-0.4	3
0.4-0.5	5
0.5-0.6	0
0.6-0.7	1
0.7-0.8	1
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
0.7556	Intermediate Similarity	NPD1549	Phase 2
0.6078	Remote Similarity	NPD1552	Clinical (unspecified phase)

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