NPASS Compound

Natural Product: NPC478955

Natural Product ID	NPC478955
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KDVJSVPEOZSZGS-SORVUCRQSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	132487957
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003422] 7,9'-epoxylignans

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 56 0 0 0 0 0 0 0 0999 V2000 -6.3350 0.0435 -0.2345 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0956 -0.1744 -1.6129 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8148 -0.0044 -2.1670 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7627 0.3658 -1.3570 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4888 0.5558 -1.8290 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3085 0.3502 -3.1919 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3420 -0.0203 -4.0073 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6224 -0.2032 -3.4958 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6546 -0.5752 -4.3196 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3081 0.9569 -1.0348 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4193 -0.1651 -0.6796 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9943 -1.2647 0.1503 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0407 -1.7256 0.9870 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2219 -1.2942 0.3712 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4229 -1.4158 1.1690 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6168 -2.4804 1.9864 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7791 -2.6359 2.7446 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7660 -1.7153 2.6867 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6262 -0.5764 1.8492 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4197 -0.4788 1.1066 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5753 0.2792 1.8122 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5062 1.1503 1.7547 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9600 -1.8160 3.4257 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7922 0.1888 0.1575 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3482 0.7085 1.4961 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4256 1.0547 2.3085 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6803 1.9652 -1.7549 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6846 3.1805 -1.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0430 1.0821 0.0741 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4354 0.0013 -0.0824 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8704 -0.7135 0.4196 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9374 0.5140 -0.3067 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3376 0.4800 -3.6541 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2202 -0.1828 -5.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7143 -1.4994 -4.7639 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6838 1.4195 -0.0993 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0248 -0.6746 -1.5830 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2409 -2.1628 -0.4852 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8576 -0.9929 0.7628 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2560 -1.7523 -0.6274 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8389 -3.2249 2.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9195 -3.5081 3.4057 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3711 0.4189 0.4799 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2651 2.2218 1.4723 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2815 0.8849 0.9395 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1140 1.2046 2.7245 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5508 -0.9873 3.5435 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5499 0.7668 -0.3505 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1546 -0.1390 2.0544 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4137 1.4948 1.4443 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4981 0.5598 3.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1840 3.9708 -1.7502 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0505 3.0652 -0.2667 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6168 3.4994 -0.6644 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 10 27 1 0 27 28 1 0 8 3 1 0 24 11 1 0 20 15 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 6 33 1 0 7 34 1 0 9 35 1 0 10 36 1 1 11 37 1 6 12 38 1 0 12 39 1 0 14 40 1 6 16 41 1 0 17 42 1 0 20 43 1 0 22 44 1 0 22 45 1 0 22 46 1 0 23 47 1 0 24 48 1 6 25 49 1 0 25 50 1 0 26 51 1 0 28 52 1 0 28 53 1 0 28 54 1 0 M END

Standard InCHIKey	KDVJSVPEOZSZGS-SORVUCRQSA-N
Standard InCHI	InChI=1S/C21H26O7/c1-25-18-8-12(4-6-16(18)23)20(27-3)15-11-28-21(14(15)10-22)13-5-7-17(24)19(9-13)26-2/h4-9,14-15,20-24H,10-11H2,1-3H3/t14-,15-,20+,21-/m1/s1
SMILES	COc1cc(ccc1O)[C@@H]([C@@H]1CO[C@H](c2ccc(c(c2)OC)O)[C@@H]1CO)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	390.17	Volume:	391.816 ? Van der Waals volume.
Dense:	0.996	LogP:	0.826 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.114 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.026 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	17.0
TPSA:	97.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.669	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.81	Fsp³:	0.429
MCE-18:	62.067 ? 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:	0.224	Fluc inhibitor:	0.339 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.021 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.187 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.231	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.275	MDCK Permeability:	-5.148
Pgp-inhibitor:	0.045	Pgp-substrate:	0.139
PAMPA:	0.164 ? 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):	0.002
20% Bioavailability (F20%):	0.085	30% Bioavailability (F30%):	0.298
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.762
Plasma Protein Binding (PPB):	73.485%	Volume Distribution (VD):	0.001
Fu:	27.341% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.332
BSEP inhibitor:	0.096

ADMET: Metabolism

CYP1A2-inhibitor:	0.969	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.999	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.968	CYP2C9-substrate:	0.012
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.432
CYP3A4-inhibitor:	0.287	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.239
HLM stability:	0.008 ? 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):

8.302

Half-life (T1/2):

2.018

ADMET: Toxicity

hERG Blockers:	0.06	hERG Blockers (10um):	0.465
Human Hepatotoxicity (H-HT):	0.802	Drug-induced Liver Injury (DILI):	0.335
AMES Toxicity:	0.79	Rat Oral Acute Toxicity:	0.367
Maximum Recommended Daily Dose:	0.219	Skin Sensitization:	0.955
Carcinogencity:	0.498	Eye Corrosion:	0.014
Eye Irritation:	0.926	Respiratory Toxicity:	0.397
Drug-induced Neurotoxicity:	0.345	Ototoxicity:	0.689
Hematotoxicity:	0.363	Drug-induced Nephrotoxicity:	0.762
Genotoxicity:	0.735	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.168	Hek293 Cytotoxicity:	0.219
BCF:	0.776 ? 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:	3.247 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.74 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.843 ? 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
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	needles	Himalayan	n.a.	PMID[16480866]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	Stem Bark	n.a.	n.a.	PMID[28240909]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	Roots	n.a.	n.a.	PMID[28581744]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7264680]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23720	Taxus wallichiana	Species	Taxaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23720	Taxus wallichiana	Species	Taxaceae	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
IC50	1

Activity Type	# Activity
Others	1

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
NPT2	Others	Unspecified	n.a.	IC50	=	42900.0	nM	PMID[28581744]

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 NPC478955 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	21589
0.1-0.2	24002
0.2-0.3	3505
0.3-0.4	541
0.4-0.5	143
0.5-0.6	43
0.6-0.7	19
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	NPC478700
0.7556	Intermediate Similarity	NPC115207
0.7556	Intermediate Similarity	NPC158079
0.7556	Intermediate Similarity	NPC228346
0.7556	Intermediate Similarity	NPC40432
0.7556	Intermediate Similarity	NPC161557
0.6939	Remote Similarity	NPC126409
0.6939	Remote Similarity	NPC99572
0.6852	Remote Similarity	NPC272
0.6852	Remote Similarity	NPC187998
0.6852	Remote Similarity	NPC77040
0.6852	Remote Similarity	NPC257582
0.6852	Remote Similarity	NPC241522
0.6852	Remote Similarity	NPC485398
0.6809	Remote Similarity	NPC242807
0.6809	Remote Similarity	NPC476266
0.6809	Remote Similarity	NPC153739
0.6607	Remote Similarity	NPC282833
0.6538	Remote Similarity	NPC27843
0.6538	Remote Similarity	NPC7171
0.6296	Remote Similarity	NPC223185
0.6102	Remote Similarity	NPC42300
0.6066	Remote Similarity	NPC287745
0.6034	Remote Similarity	NPC486558
0.6	Remote Similarity	NPC610778
0.5965	Remote Similarity	NPC88640
0.5965	Remote Similarity	NPC101153
0.5965	Remote Similarity	NPC193666
0.5965	Remote Similarity	NPC123526
0.5965	Remote Similarity	NPC608725
0.5893	Remote Similarity	NPC181049
0.58	Remote Similarity	NPC142985
0.5769	Remote Similarity	NPC469480
0.5738	Remote Similarity	NPC64201
0.5714	Remote Similarity	NPC282703
0.5714	Remote Similarity	NPC184733
0.5714	Remote Similarity	NPC128208
0.5714	Remote Similarity	NPC129570
0.5714	Remote Similarity	NPC63238
0.5714	Remote Similarity	NPC602603
0.5625	Remote Similarity	NPC470097
0.5593	Remote Similarity	NPC277804
0.5517	Remote Similarity	NPC471942
0.55	Remote Similarity	NPC145144
0.5472	Remote Similarity	NPC147379
0.5472	Remote Similarity	NPC470804
0.541	Remote Similarity	NPC67247
0.5397	Remote Similarity	NPC265154
0.5385	Remote Similarity	NPC4940
0.5333	Remote Similarity	NPC610652
0.5312	Remote Similarity	NPC25127
0.5306	Remote Similarity	NPC141765
0.5306	Remote Similarity	NPC34103
0.5294	Remote Similarity	NPC51328
0.5294	Remote Similarity	NPC209567
0.5294	Remote Similarity	NPC55158
0.5217	Remote Similarity	NPC324492
0.5217	Remote Similarity	NPC38041
0.5217	Remote Similarity	NPC22150
0.5217	Remote Similarity	NPC317053
0.5156	Remote Similarity	NPC470098
0.5156	Remote Similarity	NPC473266
0.5156	Remote Similarity	NPC471988
0.5082	Remote Similarity	NPC481088
0.5082	Remote Similarity	NPC23646
0.5082	Remote Similarity	NPC485397
0.5072	Remote Similarity	NPC114119
0.5072	Remote Similarity	NPC471415

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC478955 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4133
0.1-0.2	4880
0.2-0.3	127
0.3-0.4	9
0.4-0.5	1
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