NPASS Compound

Natural Product: NPC304594

Natural Product ID	NPC304594
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ILVXJJSXHREWRQ-NEKAXPPMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	101114359
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 74 76 0 0 0 0 0 0 0 0999 V2000 7.5127 -3.4266 -3.8061 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1669 -2.1896 -3.8732 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9567 -1.2324 -2.9188 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0988 -1.4475 -1.8621 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9073 -0.4491 -0.9044 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6010 0.7224 -1.0716 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4522 0.9527 -2.1081 C 0 0 0 0 0 0 0 0 0 0 0 0 8.6487 -0.0239 -3.0568 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5158 0.2127 -4.1116 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9900 -0.6997 0.2167 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7456 0.1620 1.1786 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8152 -0.1314 2.2884 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2499 -1.2436 2.2905 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6232 0.8342 3.2549 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7499 0.5942 4.3173 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3671 0.3561 3.7895 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8588 1.5668 3.0014 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4868 1.2730 2.5120 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2224 0.6800 1.2984 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0856 0.4157 0.8707 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1742 0.7405 1.6526 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9011 1.3422 2.8838 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6147 1.5949 3.2893 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9929 1.6686 3.6704 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8685 2.2812 4.9393 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4874 0.5066 1.2901 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9726 -0.0776 0.1327 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.7510 -1.3260 0.5782 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7978 -0.9866 1.4208 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9316 0.8834 -0.5164 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4641 0.3793 -1.8102 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8731 0.7769 -3.0132 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3575 0.3345 -4.2213 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4406 -0.5145 -4.2810 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0564 -0.9325 -3.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5385 -0.4647 -1.9171 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1443 -1.7861 -3.1920 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7681 -2.2074 -2.0039 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9113 -0.9480 -5.5115 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9731 1.1481 0.3566 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6666 -3.9475 -2.8474 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4199 -3.2380 -3.9720 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9312 -4.0734 -4.6177 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5564 -2.3911 -1.7493 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4668 1.5065 -0.3436 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9646 1.9180 -2.1617 H 0 0 0 0 0 0 0 0 0 0 0 0 9.6028 1.1558 -4.4531 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4733 -1.6461 0.2708 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2367 1.1135 1.1642 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6861 1.4567 5.0188 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0773 -0.3112 4.8654 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2417 -0.5623 3.2226 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7051 0.2503 4.6999 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5505 1.6988 2.1405 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9095 2.4767 3.6284 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0411 0.4153 0.6675 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2617 -0.0494 -0.0865 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3912 2.0653 4.2523 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2393 3.1907 4.8992 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4338 1.5171 5.6210 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8621 2.5734 5.3127 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1694 -0.3814 -0.5734 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0441 -1.9256 1.2254 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0572 -1.9163 -0.2986 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5104 -0.9063 2.3638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3742 1.8443 -0.6680 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0200 1.4438 -2.9933 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9057 0.6363 -5.1540 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0226 -0.7871 -1.0104 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9500 -1.3401 -1.3038 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1916 -2.9490 -1.4425 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7605 -2.6564 -2.2751 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9217 -0.9030 -5.6445 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2786 2.0772 0.2998 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 2 0 11 12 1 0 12 13 2 0 12 14 1 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 24 25 1 0 21 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 27 30 1 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 35 37 1 0 37 38 1 0 34 39 1 0 30 40 1 0 8 3 1 0 23 18 1 0 36 31 1 0 1 41 1 0 1 42 1 0 1 43 1 0 4 44 1 0 6 45 1 0 7 46 1 0 9 47 1 0 10 48 1 0 11 49 1 0 15 50 1 0 15 51 1 0 16 52 1 0 16 53 1 0 17 54 1 0 17 55 1 0 19 56 1 0 20 57 1 0 23 58 1 0 25 59 1 0 25 60 1 0 25 61 1 0 27 62 1 6 28 63 1 0 28 64 1 0 29 65 1 0 30 66 1 6 32 67 1 0 33 68 1 0 36 69 1 0 38 70 1 0 38 71 1 0 38 72 1 0 39 73 1 0 40 74 1 0 M END

Standard InCHIKey	ILVXJJSXHREWRQ-NEKAXPPMSA-N
Standard InCHI	InChI=1S/C30H34O10/c1-36-25-15-20(6-10-22(25)32)8-13-29(34)39-14-4-5-19-7-12-24(27(16-19)38-3)40-28(18-31)30(35)21-9-11-23(33)26(17-21)37-2/h6-13,15-17,28,30-33,35H,4-5,14,18H2,1-3H3/b13-8+/t28-,30+/m0/s1
SMILES	COc1cc(ccc1O)/C=C/C(=O)OCCCc1ccc(c(c1)OC)O[C@@H](CO)[C@@H](c1ccc(c(c1)OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	554.22	Volume:	560.668 ? Van der Waals volume.
Dense:	0.988	LogP:	2.425 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.576 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.136 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	20.0
TPSA:	144.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.132	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.421	Fsp³:	0.3
MCE-18:	42.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.908	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.08 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.655 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.054	Promiscuous compounds:	0.361

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.469	MDCK Permeability:	-5.045
Pgp-inhibitor:	0.947	Pgp-substrate:	0.01
PAMPA:	0.019 ? 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):	0.028
20% Bioavailability (F20%):	0.612	30% Bioavailability (F30%):	0.793
50% Bioavailability (F50%):	0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.107
Plasma Protein Binding (PPB):	92.394%	Volume Distribution (VD):	-0.024
Fu:	7.002% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.529
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.71	CYP2C19-substrate:	0.008
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.894
CYP2D6-inhibitor:	0.452	CYP2D6-substrate:	0.726
CYP3A4-inhibitor:	0.017	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.003 ? 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):

4.954

Half-life (T1/2):

1.413

ADMET: Toxicity

hERG Blockers:	0.228	hERG Blockers (10um):	0.446
Human Hepatotoxicity (H-HT):	0.654	Drug-induced Liver Injury (DILI):	0.372
AMES Toxicity:	0.538	Rat Oral Acute Toxicity:	0.047
Maximum Recommended Daily Dose:	0.104	Skin Sensitization:	0.994
Carcinogencity:	0.176	Eye Corrosion:	0.0
Eye Irritation:	0.564	Respiratory Toxicity:	0.055
Drug-induced Neurotoxicity:	0.447	Ototoxicity:	0.494
Hematotoxicity:	0.034	Drug-induced Nephrotoxicity:	0.672
Genotoxicity:	0.068	RPMI-8226 Immunitoxicity:	0.264
A549 Cytotoxicity:	0.618	Hek293 Cytotoxicity:	0.7
BCF:	1.066 ? 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:	3.906 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.114 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.733 ? 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
NPO22589	Clematis armandii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23035	Clematis montana	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22589	Clematis armandii	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]

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 NPC304594 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	14692
0.1-0.2	30412
0.2-0.3	4003
0.3-0.4	639
0.4-0.5	71
0.5-0.6	22
0.6-0.7	14
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8267	Intermediate Similarity	NPC143120
0.7	Intermediate Similarity	NPC274960
0.6875	Remote Similarity	NPC482415
0.6875	Remote Similarity	NPC482416
0.6813	Remote Similarity	NPC485396
0.6813	Remote Similarity	NPC485394
0.6813	Remote Similarity	NPC485395
0.662	Remote Similarity	NPC111247
0.662	Remote Similarity	NPC292056
0.6081	Remote Similarity	NPC147821
0.6081	Remote Similarity	NPC319625
0.6081	Remote Similarity	NPC183181
0.6081	Remote Similarity	NPC41706
0.6	Remote Similarity	NPC476387
0.6	Remote Similarity	NPC237594
0.6	Remote Similarity	NPC119060
0.5581	Remote Similarity	NPC473909
0.5556	Remote Similarity	NPC70752
0.5526	Remote Similarity	NPC163332
0.5455	Remote Similarity	NPC470413
0.5405	Remote Similarity	NPC9370
0.5405	Remote Similarity	NPC287495
0.5393	Remote Similarity	NPC115203
0.5341	Remote Similarity	NPC138738
0.5333	Remote Similarity	NPC293701
0.527	Remote Similarity	NPC83062
0.5263	Remote Similarity	NPC16208
0.5263	Remote Similarity	NPC601893
0.5256	Remote Similarity	NPC481839
0.5217	Remote Similarity	NPC125495
0.507	Remote Similarity	NPC202474
0.5065	Remote Similarity	NPC60517
0.5065	Remote Similarity	NPC58607
0.5065	Remote Similarity	NPC146886
0.5065	Remote Similarity	NPC191037
0.5065	Remote Similarity	NPC20443
0.5065	Remote Similarity	NPC178284
0.5063	Remote Similarity	NPC267291

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC304594 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3760
0.1-0.2	5155
0.2-0.3	226
0.3-0.4	9
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