NPASS Compound

Natural Product: NPC224412

Natural Product ID	NPC224412
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PFCOJAPJHVVASV-LSDHHAIUSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	14703253
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003424] 9,9'-epoxylignans [CHEMONTID:0001613] Dibenzylbutyrolactone 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 50 53 0 0 0 0 0 0 0 0999 V2000 -2.3033 -2.6439 -0.7242 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5709 -1.5701 -1.5982 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4991 -0.2784 -1.0961 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1791 0.0051 0.2141 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1137 1.3104 0.6933 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7661 1.5168 2.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3081 1.7061 2.3935 C 0 0 2 0 0 0 0 0 0 0 0 0 0.5628 0.5435 1.9861 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1593 0.8765 0.6408 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0320 -0.1552 0.0824 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5907 -1.1932 -0.7140 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4783 -2.1268 -1.2065 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8279 -2.0824 -0.9406 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2798 -1.0542 -0.1491 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3813 -0.1104 0.3485 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6437 -1.1855 -0.0023 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1067 -2.2173 -0.8453 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9336 -2.8437 -1.2756 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7015 0.7110 2.9968 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0301 1.1258 4.1810 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1902 1.6775 3.8765 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0628 2.0896 4.6947 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3799 2.3186 -0.1861 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7019 2.0466 -1.5026 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7653 0.7520 -1.9720 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0960 0.5105 -3.3176 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4609 0.3434 -3.6545 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9743 3.0697 -2.4041 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3226 -2.5812 -0.2307 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3384 -3.6184 -1.2637 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0635 -2.6764 0.0867 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9748 -0.8138 0.8861 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2856 2.4321 2.4468 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1246 0.6842 2.7451 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0898 2.6757 2.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0747 -0.4204 2.0565 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4145 1.1929 -0.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7908 1.7976 0.8309 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5323 -1.2236 -0.9196 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1215 -2.9418 -1.8337 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8284 0.6675 0.9619 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7028 -1.7619 -1.6457 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7501 -2.8713 -0.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4054 1.4983 2.6656 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2780 -0.2167 3.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3343 3.3290 0.1648 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8769 1.3760 -3.7761 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0474 -0.1422 -2.8593 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5793 -0.2166 -4.5978 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3972 3.1858 -3.2121 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 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 1 0 8 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 5 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 1 0 24 28 1 0 25 3 1 0 21 7 1 0 15 10 1 0 18 13 1 0 1 29 1 0 1 30 1 0 1 31 1 0 4 32 1 0 6 33 1 0 6 34 1 0 7 35 1 6 8 36 1 6 9 37 1 0 9 38 1 0 11 39 1 0 12 40 1 0 15 41 1 0 17 42 1 0 17 43 1 0 19 44 1 0 19 45 1 0 23 46 1 0 27 47 1 0 27 48 1 0 27 49 1 0 28 50 1 0 M END

Standard InCHIKey	PFCOJAPJHVVASV-LSDHHAIUSA-N
Standard InCHI	InChI=1S/C21H22O7/c1-24-19-9-13(7-16(22)20(19)25-2)6-15-14(10-26-21(15)23)5-12-3-4-17-18(8-12)28-11-27-17/h3-4,7-9,14-15,22H,5-6,10-11H2,1-2H3/t14-,15+/m0/s1
SMILES	COc1cc(C[C@@H]2[C@@H](Cc3ccc4c(c3)OCO4)COC2=O)cc(c1OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	386.14	Volume:	380.623 ? Van der Waals volume.
Dense:	1.014	LogP:	2.448 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.46 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.965 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	22.0
TPSA:	83.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.764	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.349	Fsp³:	0.381
MCE-18:	72.069 ? 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:	0.405	Fluc inhibitor:	0.379 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.028 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.312 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.23	Promiscuous compounds:	0.371

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.009	MDCK Permeability:	-4.73
Pgp-inhibitor:	0.434	Pgp-substrate:	0.01
PAMPA:	0.199 ? 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):	0.001
20% Bioavailability (F20%):	0.424	30% Bioavailability (F30%):	0.025
50% Bioavailability (F50%):	0.511

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.182	MRP1:	0.788
Plasma Protein Binding (PPB):	98.215%	Volume Distribution (VD):	-0.313
Fu:	1.887% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.918
OATP1B3 inhibitor:	0.734	BCRP inhibitor:	0.005
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.4	CYP1A2-substrate:	0.736
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.994
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.068
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.934 ? 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):

2.876

Half-life (T1/2):

1.54

ADMET: Toxicity

hERG Blockers:	0.18	hERG Blockers (10um):	0.573
Human Hepatotoxicity (H-HT):	0.949	Drug-induced Liver Injury (DILI):	0.98
AMES Toxicity:	0.795	Rat Oral Acute Toxicity:	0.32
Maximum Recommended Daily Dose:	0.612	Skin Sensitization:	0.863
Carcinogencity:	0.821	Eye Corrosion:	0.003
Eye Irritation:	0.877	Respiratory Toxicity:	0.352
Drug-induced Neurotoxicity:	0.802	Ototoxicity:	0.673
Hematotoxicity:	0.669	Drug-induced Nephrotoxicity:	0.905
Genotoxicity:	0.985	RPMI-8226 Immunitoxicity:	0.259
A549 Cytotoxicity:	0.42	Hek293 Cytotoxicity:	0.544
BCF:	1.392 ? 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:	3.889 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.496 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.765 ? 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
NPO10903	Sinopodophyllum hexandrum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26359402]
NPO10903	Sinopodophyllum hexandrum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10903	Sinopodophyllum hexandrum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10903	Sinopodophyllum hexandrum	Species	Berberidaceae	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 NPC224412 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	21375
0.1-0.2	25029
0.2-0.3	2991
0.3-0.4	336
0.4-0.5	79
0.5-0.6	21
0.6-0.7	13
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
0.7705	Intermediate Similarity	NPC282291
0.7705	Intermediate Similarity	NPC166137
0.7679	Intermediate Similarity	NPC205915
0.7667	Intermediate Similarity	NPC145569
0.7593	Intermediate Similarity	NPC110958
0.7593	Intermediate Similarity	NPC19890
0.7414	Intermediate Similarity	NPC176586
0.7414	Intermediate Similarity	NPC210354
0.7288	Intermediate Similarity	NPC191158
0.7288	Intermediate Similarity	NPC177644
0.6515	Remote Similarity	NPC216223
0.6429	Remote Similarity	NPC223807
0.6349	Remote Similarity	NPC5310
0.6349	Remote Similarity	NPC300776
0.6349	Remote Similarity	NPC176814
0.6349	Remote Similarity	NPC4982
0.6349	Remote Similarity	NPC606629
0.6271	Remote Similarity	NPC92693
0.6269	Remote Similarity	NPC174512
0.625	Remote Similarity	NPC293757
0.625	Remote Similarity	NPC668
0.6167	Remote Similarity	NPC40237
0.6	Remote Similarity	NPC211386
0.597	Remote Similarity	NPC487679
0.597	Remote Similarity	NPC56184
0.597	Remote Similarity	NPC487678
0.5965	Remote Similarity	NPC476748
0.5902	Remote Similarity	NPC68779
0.5902	Remote Similarity	NPC108598
0.5902	Remote Similarity	NPC143895
0.5846	Remote Similarity	NPC106920
0.5846	Remote Similarity	NPC15811
0.5606	Remote Similarity	NPC3982
0.5556	Remote Similarity	NPC478703
0.5556	Remote Similarity	NPC478704
0.5538	Remote Similarity	NPC273657
0.5517	Remote Similarity	NPC72796
0.5417	Remote Similarity	NPC478705
0.5345	Remote Similarity	NPC600801
0.5323	Remote Similarity	NPC192255
0.5323	Remote Similarity	NPC474288
0.525	Remote Similarity	NPC245615
0.5211	Remote Similarity	NPC169973
0.5156	Remote Similarity	NPC158737

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC224412 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4111
0.1-0.2	4868
0.2-0.3	159
0.3-0.4	12
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