NPASS Compound

Natural Product: NPC265431

Natural Product ID	NPC265431
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HJQLSMCJAZKMGU-SDWXPCGYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	14583617
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones [CHEMONTID:0000047] Podophyllotoxins

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 61 65 0 0 0 0 0 0 0 0999 V2000 -5.5819 -1.4938 -2.6947 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1125 -1.2306 -2.5356 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3742 -1.0640 -3.5121 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5636 -1.1718 -1.2626 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2173 -0.9346 -0.9965 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6787 -2.0877 -0.2519 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7527 -3.4717 -0.6882 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8110 -4.0788 0.2547 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0473 -3.0171 0.8583 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4402 -3.1771 1.9853 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1163 -2.0130 -0.1637 C 0 0 2 0 0 0 0 0 0 0 0 0 0.3377 -0.6624 -0.1348 C 0 0 2 0 0 0 0 0 0 0 0 0 1.7182 -0.3043 0.1072 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6556 -1.2073 0.4925 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9716 -0.7578 0.7089 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3368 0.5604 0.5427 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3698 1.4598 0.1506 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0932 1.0135 -0.0571 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7351 2.7854 -0.0174 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7449 3.7079 -0.4193 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6535 0.9736 0.7662 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5272 0.9305 -0.3464 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9644 -1.6408 1.1038 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7403 -3.0183 1.3136 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6691 0.2560 0.5128 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3499 1.1637 1.4883 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3372 2.0168 1.9863 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6156 1.9314 1.4884 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9246 0.9923 0.4879 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9726 0.1604 0.0013 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2171 0.9120 -0.0103 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4778 1.7835 -1.1243 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3827 2.8702 2.1383 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6293 3.5214 3.1493 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3155 3.0143 2.9511 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7816 -2.5947 -2.6691 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1544 -1.0643 -1.8443 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9815 -1.0353 -3.6184 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6551 -0.7724 -1.9405 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0490 -2.0162 0.8112 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3312 -3.5775 -1.7127 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7370 -3.9697 -0.5808 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1965 -2.5406 -1.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2069 -0.3015 -1.2556 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4862 -2.2639 0.6373 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3667 1.7812 -0.3692 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3174 3.4699 -1.4174 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8890 3.6453 0.2999 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2059 4.7157 -0.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9923 1.1536 -1.2987 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9285 -0.1058 -0.4333 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3298 1.6887 -0.2597 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2251 -3.4133 0.4323 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7421 -3.4993 1.3641 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2282 -3.1998 2.2710 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6580 1.2173 1.8760 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7765 1.5913 -1.9575 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5326 1.7382 -1.4377 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2831 2.8492 -0.8170 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9670 3.1599 4.1428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6656 4.6220 3.0672 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 16 21 1 0 21 22 1 0 15 23 1 0 23 24 1 0 12 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 29 31 1 0 31 32 1 0 28 33 1 0 33 34 1 0 34 35 1 0 30 5 1 0 11 6 1 0 18 13 1 0 30 25 1 0 35 27 1 0 1 36 1 0 1 37 1 0 1 38 1 0 5 39 1 6 6 40 1 1 7 41 1 0 7 42 1 0 11 43 1 6 12 44 1 6 14 45 1 0 18 46 1 0 20 47 1 0 20 48 1 0 20 49 1 0 22 50 1 0 22 51 1 0 22 52 1 0 24 53 1 0 24 54 1 0 24 55 1 0 26 56 1 0 32 57 1 0 32 58 1 0 32 59 1 0 34 60 1 0 34 61 1 0 M END

Standard InCHIKey	HJQLSMCJAZKMGU-SDWXPCGYSA-N
Standard InCHI	InChI=1S/C25H26O10/c1-11(26)35-21-14-9-32-25(27)19(14)18(12-6-15(28-2)22(30-4)16(7-12)29-3)13-8-17-23(34-10-33-17)24(31-5)20(13)21/h6-8,14,18-19,21H,9-10H2,1-5H3/t14-,18+,19-,21+/m0/s1
SMILES	CC(=O)O[C@@H]1[C@H]2COC(=O)[C@@H]2[C@H](c2cc(c(c(c2)OC)OC)OC)c2cc3c(c(c12)OC)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	486.15	Volume:	464.984 ? Van der Waals volume.
Dense:	1.046	LogP:	2.018 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.221 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.362 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	27.0
TPSA:	107.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.566	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.013	Fsp³:	0.44
MCE-18:	100.0 ? 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:	0.228	Fluc inhibitor:	0.193 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.223 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.258 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.209	Promiscuous compounds:	0.41

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.078	MDCK Permeability:	-4.832
Pgp-inhibitor:	0.756	Pgp-substrate:	0.003
PAMPA:	0.042 ? 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):	0.0
20% Bioavailability (F20%):	0.006	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.145

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.963	MRP1:	0.998
Plasma Protein Binding (PPB):	96.162%	Volume Distribution (VD):	-0.386
Fu:	4.35% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.792
OATP1B3 inhibitor:	0.658	BCRP inhibitor:	0.001
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.011	CYP1A2-substrate:	0.125
CYP2C19-inhibitor:	0.928	CYP2C19-substrate:	0.094
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.077
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.991
CYP3A4-inhibitor:	0.996	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.001	CYP2C8-inhibitor:	0.965
HLM stability:	0.759 ? 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):

4.183

Half-life (T1/2):

1.873

ADMET: Toxicity

hERG Blockers:	0.126	hERG Blockers (10um):	0.554
Human Hepatotoxicity (H-HT):	0.901	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.902	Rat Oral Acute Toxicity:	0.856
Maximum Recommended Daily Dose:	0.832	Skin Sensitization:	0.998
Carcinogencity:	0.939	Eye Corrosion:	0.0
Eye Irritation:	0.071	Respiratory Toxicity:	0.91
Drug-induced Neurotoxicity:	0.951	Ototoxicity:	0.779
Hematotoxicity:	0.98	Drug-induced Nephrotoxicity:	0.997
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.766
A549 Cytotoxicity:	0.947	Hek293 Cytotoxicity:	0.674
BCF:	1.054 ? 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:	3.404 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.006 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.108 ? 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
NPO5212	Ascophyllum nodosum	Species	Fucaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11121113]
NPO5212	Ascophyllum nodosum	Species	Fucaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7816	Cystoseira adriatica	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9432	Galium fagetorum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5042	Salpichroa diffusa	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12515	Xeromphis nilotica	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO549	Musa X paradisiaca	Strain	Musaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO549	Musa X paradisiaca	Strain	Musaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO549	Musa X paradisiaca	Strain	Musaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9432	Galium fagetorum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5042	Salpichroa diffusa	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7816	Cystoseira adriatica	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO549	Musa X paradisiaca	Strain	Musaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5212	Ascophyllum nodosum	Species	Fucaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12515	Xeromphis nilotica	n.a.	n.a.	n.a.	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 NPC265431 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	24985
0.1-0.2	23614
0.2-0.3	987
0.3-0.4	186
0.4-0.5	58
0.5-0.6	23
0.6-0.7	2
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
0.7742	Intermediate Similarity	NPC210642
0.7742	Intermediate Similarity	NPC13985
0.75	Intermediate Similarity	NPC273578
0.6364	Remote Similarity	NPC149505
0.6119	Remote Similarity	NPC480477
0.5942	Remote Similarity	NPC207584
0.5942	Remote Similarity	NPC19947
0.5732	Remote Similarity	NPC100465
0.5672	Remote Similarity	NPC239890
0.5672	Remote Similarity	NPC209411
0.5588	Remote Similarity	NPC80230
0.5588	Remote Similarity	NPC104024
0.5588	Remote Similarity	NPC101755
0.5588	Remote Similarity	NPC304687
0.5588	Remote Similarity	NPC65574
0.5556	Remote Similarity	NPC96593
0.5507	Remote Similarity	NPC262455
0.5507	Remote Similarity	NPC177476
0.5429	Remote Similarity	NPC237946
0.5429	Remote Similarity	NPC32373
0.5397	Remote Similarity	NPC151423
0.5366	Remote Similarity	NPC152424
0.5238	Remote Similarity	NPC218841
0.5135	Remote Similarity	NPC119910
0.5114	Remote Similarity	NPC306475
0.5067	Remote Similarity	NPC288149
0.5067	Remote Similarity	NPC115281
0.5067	Remote Similarity	NPC470637

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC265431 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5523
0.1-0.2	3564
0.2-0.3	51
0.3-0.4	4
0.4-0.5	4
0.5-0.6	4
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
0.5455	Remote Similarity	NPD6234	Discontinued
0.5429	Remote Similarity	NPD4965	Approved
0.5429	Remote Similarity	NPD4966	Phase 4
0.5429	Remote Similarity	NPD4967	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