NPASS Compound

Natural Product: NPC271362

Natural Product ID	NPC271362
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	CICMVLOHBZPXIT-ZNYHDOEXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	21632947
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans

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 49 52 0 0 0 0 0 0 0 0999 V2000 5.1437 2.8073 2.3359 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5737 1.4815 2.1051 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8474 0.5717 1.3543 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6338 0.8523 0.7520 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9471 -0.0909 0.0121 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4670 -1.3513 -0.1434 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6870 -1.6464 0.4577 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3700 -0.6941 1.1990 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6008 -1.0317 1.7908 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6812 0.2518 -0.6157 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7923 -0.9329 -0.9266 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5127 -1.8219 0.2386 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8877 -2.0490 0.2186 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3783 -0.7881 0.0225 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.8071 -0.7572 -0.3493 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2661 -1.6392 -1.3016 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6118 -1.6345 -1.6745 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4997 -0.7516 -1.0988 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0372 0.1437 -0.1331 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6969 0.1257 0.2258 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9565 1.0176 0.4255 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.6335 1.9635 1.3995 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8528 -0.7416 -1.4687 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5539 -0.2145 -1.0755 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2132 1.2151 -0.7841 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8515 1.0857 0.1455 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0852 -0.4094 -2.3445 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2189 2.8072 2.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9672 3.3712 2.8021 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9835 3.2725 1.3266 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2537 1.8668 0.8990 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0055 -2.1466 -0.7089 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0926 -2.6301 0.3366 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2992 -1.4177 1.1471 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8418 0.7815 -1.5777 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0824 -1.4556 -1.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7588 -1.3931 1.2138 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9267 -2.8667 0.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2068 -0.2048 0.9509 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5801 -2.3369 -1.7609 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9541 -2.3349 -2.4244 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3385 0.8299 0.9838 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8671 1.5600 2.1181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2064 2.8926 0.9704 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5054 2.2270 2.0441 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0586 -0.2074 -2.3162 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2168 1.7229 -1.6674 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0463 1.7849 -0.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5120 -1.0844 -2.8020 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 5 10 1 0 10 11 1 0 11 12 1 0 12 13 1 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 19 21 1 0 21 22 1 0 18 23 1 0 14 24 1 0 24 25 1 0 25 26 1 0 24 27 1 6 8 3 1 0 26 10 1 0 24 11 1 0 20 15 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 7 33 1 0 9 34 1 0 10 35 1 6 11 36 1 6 12 37 1 0 12 38 1 0 14 39 1 1 16 40 1 0 17 41 1 0 20 42 1 0 22 43 1 0 22 44 1 0 22 45 1 0 23 46 1 0 25 47 1 0 25 48 1 0 27 49 1 0 M END

Standard InCHIKey	CICMVLOHBZPXIT-ZNYHDOEXSA-N
Standard InCHI	InChI=1S/C20H22O7/c1-24-16-7-11(3-5-14(16)21)18-13-9-26-19(20(13,23)10-27-18)12-4-6-15(22)17(8-12)25-2/h3-8,13,18-19,21-23H,9-10H2,1-2H3/t13-,18+,19-,20-/m1/s1
SMILES	COc1cc(ccc1O)[C@H]1[C@H]2CO[C@H](c3ccc(c(c3)OC)O)[C@]2(CO1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	374.14	Volume:	365.963 ? Van der Waals volume.
Dense:	1.022	LogP:	1.1 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.355 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.921 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	21.0
TPSA:	97.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.755	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.882	Fsp³:	0.4
MCE-18:	82.286 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.136	Fluc inhibitor:	0.34 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.03 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.077 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.221	Promiscuous compounds:	0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.591	MDCK Permeability:	-4.902
Pgp-inhibitor:	0.002	Pgp-substrate:	0.309
PAMPA:	0.131 ? 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):	0.009
20% Bioavailability (F20%):	0.842	30% Bioavailability (F30%):	0.602
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.966
Plasma Protein Binding (PPB):	76.829%	Volume Distribution (VD):	-0.205
Fu:	25.375% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.941
OATP1B3 inhibitor:	0.951	BCRP inhibitor:	0.189
BSEP inhibitor:	0.054

ADMET: Metabolism

CYP1A2-inhibitor:	0.993	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.673	CYP2C9-substrate:	0.011
CYP2D6-inhibitor:	0.156	CYP2D6-substrate:	0.481
CYP3A4-inhibitor:	0.901	CYP3A4-substrate:	0.668
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.237
HLM stability:	0.004 ? 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):

6.474

Half-life (T1/2):

2.693

ADMET: Toxicity

hERG Blockers:	0.05	hERG Blockers (10um):	0.321
Human Hepatotoxicity (H-HT):	0.651	Drug-induced Liver Injury (DILI):	0.589
AMES Toxicity:	0.929	Rat Oral Acute Toxicity:	0.486
Maximum Recommended Daily Dose:	0.443	Skin Sensitization:	0.993
Carcinogencity:	0.685	Eye Corrosion:	0.128
Eye Irritation:	0.988	Respiratory Toxicity:	0.558
Drug-induced Neurotoxicity:	0.52	Ototoxicity:	0.231
Hematotoxicity:	0.292	Drug-induced Nephrotoxicity:	0.444
Genotoxicity:	0.76	RPMI-8226 Immunitoxicity:	0.19
A549 Cytotoxicity:	0.753	Hek293 Cytotoxicity:	0.659
BCF:	1.033 ? 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:	3.354 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.327 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.787 ? 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
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30739	Forsythia suspense	Species	Oleaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14108	Nardostachys jatamansi	Species	Caprifoliaceae	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 NPC271362 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	22212
0.1-0.2	23809
0.2-0.3	3244
0.3-0.4	482
0.4-0.5	71
0.5-0.6	29
0.6-0.7	9
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC181049
0.6852	Remote Similarity	NPC207400
0.6479	Remote Similarity	NPC112861
0.6275	Remote Similarity	NPC4940
0.6078	Remote Similarity	NPC115207
0.6078	Remote Similarity	NPC158079
0.6078	Remote Similarity	NPC228346
0.6078	Remote Similarity	NPC40432
0.6078	Remote Similarity	NPC161557
0.6038	Remote Similarity	NPC147379
0.5893	Remote Similarity	NPC478955
0.5893	Remote Similarity	NPC478700
0.5873	Remote Similarity	NPC471988
0.5862	Remote Similarity	NPC101807
0.5636	Remote Similarity	NPC126409
0.5636	Remote Similarity	NPC99572
0.5574	Remote Similarity	NPC277804
0.5574	Remote Similarity	NPC23646
0.5574	Remote Similarity	NPC485397
0.5472	Remote Similarity	NPC242807
0.5472	Remote Similarity	NPC153739
0.5455	Remote Similarity	NPC469480
0.5385	Remote Similarity	NPC282703
0.5385	Remote Similarity	NPC184733
0.5385	Remote Similarity	NPC128208
0.5385	Remote Similarity	NPC129570
0.5385	Remote Similarity	NPC63238
0.5385	Remote Similarity	NPC602603
0.5345	Remote Similarity	NPC27843
0.5345	Remote Similarity	NPC7171
0.5185	Remote Similarity	NPC142985
0.5167	Remote Similarity	NPC223185
0.5167	Remote Similarity	NPC610778
0.5161	Remote Similarity	NPC272
0.5161	Remote Similarity	NPC187998
0.5161	Remote Similarity	NPC77040
0.5161	Remote Similarity	NPC257582
0.5161	Remote Similarity	NPC241522
0.5161	Remote Similarity	NPC485398

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC271362 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4358
0.1-0.2	4698
0.2-0.3	91
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