NPASS Compound

Natural Product: NPC5948

Natural Product ID	NPC5948
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	OCZHVLYTYFWOAX-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10646095
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 58 61 0 0 0 0 0 0 0 0999 V2000 5.3701 -0.7614 1.3797 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1799 0.1393 0.3646 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4281 -0.1366 -0.9666 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2178 0.8421 -2.0378 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7926 0.7529 -2.5987 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8459 1.0273 -1.4839 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3614 0.0011 -0.6890 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4837 0.2304 0.3495 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0527 1.5107 0.6348 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5264 2.5420 -0.1479 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4060 2.3003 -1.1863 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1699 1.7100 1.6853 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1905 1.6582 1.4237 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6797 1.4118 0.1361 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0372 1.3683 -0.0820 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5288 1.1074 -1.4457 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6815 -0.4069 -1.6016 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6553 -0.9266 -0.5945 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9980 -0.9787 -0.9521 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9253 -1.4496 -0.0563 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5097 -1.8631 1.1832 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1853 -1.8123 1.5374 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2533 -1.3435 0.6487 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7929 -2.2476 2.8256 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8785 1.5680 0.9706 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4048 1.8157 2.2651 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0461 1.8587 2.4804 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5701 2.1025 3.7541 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8979 -1.4150 -1.2542 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0931 -2.3243 -0.2572 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8383 -2.0266 1.0664 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5659 -3.5989 -0.5823 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1574 -0.4886 2.4134 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8153 1.1216 0.6169 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9592 0.7101 -2.8470 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3812 1.8592 -1.6096 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6469 1.4375 -3.4325 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6425 -0.3087 -2.9049 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6811 -1.0003 -0.8906 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1151 -0.5954 0.9630 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1911 3.5450 0.0727 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7814 3.1162 -1.8063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9814 1.2591 -0.6691 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5009 1.6107 -1.5864 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8525 1.4740 -2.2230 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7132 -0.9180 -1.4322 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0008 -0.6377 -2.6312 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2738 -0.6387 -1.9469 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9636 -1.5033 -0.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2345 -2.2464 1.9234 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2158 -1.2936 0.8997 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4549 -2.3403 3.5689 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9410 1.5407 0.8353 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0930 1.9714 3.0858 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7034 1.7645 4.1120 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1008 -1.6615 -2.2812 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0008 -2.7674 1.8486 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5634 -3.8071 -0.5507 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 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 9 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 15 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 3 29 2 0 29 30 1 0 30 31 2 0 30 32 1 0 31 1 1 0 11 6 1 0 27 13 1 0 23 18 1 0 1 33 1 0 2 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 7 39 1 0 8 40 1 0 10 41 1 0 11 42 1 0 14 43 1 0 16 44 1 0 16 45 1 0 17 46 1 0 17 47 1 0 19 48 1 0 20 49 1 0 21 50 1 0 23 51 1 0 24 52 1 0 25 53 1 0 26 54 1 0 28 55 1 0 29 56 1 0 31 57 1 0 32 58 1 0 M END

Standard InCHIKey	OCZHVLYTYFWOAX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C28H26O4/c29-24-5-1-3-21(17-24)8-7-20-11-14-26(15-12-20)32-28-19-23(13-16-27(28)31)10-9-22-4-2-6-25(30)18-22/h1-6,11-19,29-31H,7-10H2
SMILES	c1cc(CCc2ccc(cc2)Oc2cc(CCc3cccc(c3)O)ccc2O)cc(c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	426.18	Volume:	462.142 ? Van der Waals volume.
Dense:	0.922	LogP:	5.107 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.752 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.863 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	24.0
TPSA:	69.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.315	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.192	Fsp³:	0.143
MCE-18:	21.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.645 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.042 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.438 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.656	Promiscuous compounds:	0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.947	MDCK Permeability:	-4.791
Pgp-inhibitor:	0.472	Pgp-substrate:	0.013
PAMPA:	0.189 ? 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):	0.033
20% Bioavailability (F20%):	0.982	30% Bioavailability (F30%):	0.974
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.047
Plasma Protein Binding (PPB):	98.091%	Volume Distribution (VD):	0.018
Fu:	1.13% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.973
OATP1B3 inhibitor:	0.832	BCRP inhibitor:	0.137
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.968	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.541	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.578
CYP2D6-inhibitor:	0.735	CYP2D6-substrate:	0.91
CYP3A4-inhibitor:	0.86	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.009	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

10.204

Half-life (T1/2):

0.745

ADMET: Toxicity

hERG Blockers:	0.922	hERG Blockers (10um):	0.969
Human Hepatotoxicity (H-HT):	0.701	Drug-induced Liver Injury (DILI):	0.05
AMES Toxicity:	0.549	Rat Oral Acute Toxicity:	0.064
Maximum Recommended Daily Dose:	0.796	Skin Sensitization:	0.928
Carcinogencity:	0.09	Eye Corrosion:	0.001
Eye Irritation:	0.728	Respiratory Toxicity:	0.312
Drug-induced Neurotoxicity:	0.272	Ototoxicity:	0.772
Hematotoxicity:	0.125	Drug-induced Nephrotoxicity:	0.506
Genotoxicity:	0.395	RPMI-8226 Immunitoxicity:	0.071
A549 Cytotoxicity:	0.927	Hek293 Cytotoxicity:	0.975
BCF:	1.751 ? 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:	5.47 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.797 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.708 ? 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
NPO12644	Lunularia cruciata	Species	Lunulariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21625478]
NPO12644	Lunularia cruciata	Species	Lunulariaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30848895]
NPO12644	Lunularia cruciata	Species	Lunulariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12644	Lunularia cruciata	Species	Lunulariaceae	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	5
ED50	1

Activity Type	# Activity
Cell line	4
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT670	Individual protein	Thrombin	Homo sapiens	IC50	=	18000.0	nM	PMID[32142276]
NPT670	Individual protein	Thrombin	Homo sapiens	IC50	=	18000.0	nM	PMID[29019405]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	40000.0	nM	PMID[30848895]
NPT81	Cell line	A549	Homo sapiens	IC50	=	25000.0	nM	PMID[30848895]
NPT91	Cell line	KB	Homo sapiens	ED50	=	12.5	ug ml-1	PMID[32142276]
NPT171	Cell line	MRC5	Homo sapiens	IC50	=	7.46	ug.mL-1	PMID[32142276]

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 NPC5948 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	25805
0.1-0.2	20084
0.2-0.3	3643
0.3-0.4	249
0.4-0.5	39
0.5-0.6	17
0.6-0.7	11
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8542	High Similarity	NPC17837
0.7708	Intermediate Similarity	NPC599909
0.7708	Intermediate Similarity	NPC604545
0.7292	Intermediate Similarity	NPC131128
0.7037	Intermediate Similarity	NPC226193
0.7037	Intermediate Similarity	NPC601081
0.6923	Remote Similarity	NPC474134
0.6667	Remote Similarity	NPC86947
0.6607	Remote Similarity	NPC73656
0.6491	Remote Similarity	NPC606516
0.6481	Remote Similarity	NPC601463
0.6429	Remote Similarity	NPC483726
0.6364	Remote Similarity	NPC134431
0.6364	Remote Similarity	NPC156854
0.6207	Remote Similarity	NPC599974
0.614	Remote Similarity	NPC610261
0.6034	Remote Similarity	NPC606874
0.5902	Remote Similarity	NPC474390
0.5902	Remote Similarity	NPC210655
0.5902	Remote Similarity	NPC601376
0.5862	Remote Similarity	NPC483725
0.5738	Remote Similarity	NPC141023
0.5614	Remote Similarity	NPC304630
0.537	Remote Similarity	NPC485986
0.5349	Remote Similarity	NPC274678
0.5172	Remote Similarity	NPC127389
0.5172	Remote Similarity	NPC290451
0.5172	Remote Similarity	NPC17109
0.5161	Remote Similarity	NPC66840
0.5122	Remote Similarity	NPC599916
0.5116	Remote Similarity	NPC609251
0.5102	Remote Similarity	NPC109828
0.5098	Remote Similarity	NPC247922
0.5079	Remote Similarity	NPC483727

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC5948 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4063
0.1-0.2	4852
0.2-0.3	229
0.3-0.4	6
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