NPASS Compound

Natural Product: NPC43065

Natural Product ID	NPC43065
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(-)-(7R,8S,7''s,8''r)-3,3'',5,5'-Tetramethoxy-4''-Hydroxy-4',7-Epoxy-8',9'-Dinor-4,8''-Oxy-8,3'-Sesquineolignan-7'',9,9''-Triol-7'-Al
IUPAC Name	(2R,3S)-2-[4-[(1S,2R)-1,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3,5-dimethoxyphenyl]-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-carbaldehyde
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1797769
PubChem CID	53356209
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 72 75 0 0 0 0 0 0 0 0999 V2000 3.7708 -1.7386 -2.7410 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0722 -0.6636 -2.2530 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9188 -0.6831 -0.7416 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2422 -0.5651 -0.0490 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8671 0.7687 -0.1470 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6362 1.6801 0.8626 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1833 2.9290 0.8548 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9931 3.2731 -0.2085 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2368 2.3629 -1.2388 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6758 1.1066 -1.2133 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0520 2.7515 -2.2806 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3743 1.8810 -3.3699 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5509 4.5569 -0.2091 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1615 -1.5370 -0.3704 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2415 -1.8768 -0.4021 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8887 -1.8123 -0.0703 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1208 -2.1268 -0.9531 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2058 -2.5346 -2.2265 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8524 -2.8684 -3.1165 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4507 -2.0283 -0.5348 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7890 -1.6278 0.7276 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7752 -1.3221 1.5889 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5634 -1.4019 1.2300 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5750 -1.0901 2.1176 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2558 -0.6784 3.4211 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2493 -1.5677 1.0301 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9853 -1.1634 -0.0798 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8328 -0.1302 0.2259 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6584 0.2321 1.5261 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6039 -0.6314 2.1185 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1281 -1.3839 3.3302 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1486 -2.2521 3.7821 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4125 1.2665 2.0678 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3416 1.9281 1.2825 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5460 1.5900 -0.0347 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7914 0.5567 -0.5729 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9565 0.1935 -1.8456 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5682 0.3446 -3.0059 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0865 3.0114 1.9218 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9560 3.6318 1.2177 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2567 -2.4309 -3.1894 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0616 -0.6523 -2.6927 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5546 0.2766 -2.5978 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2923 0.1827 -0.4887 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0242 -0.7496 1.0576 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9987 1.3940 1.6826 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0025 3.6373 1.6523 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8435 0.3676 -1.9886 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2927 1.3383 -3.0306 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5869 1.1763 -3.6239 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6660 2.4317 -4.2668 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4913 4.6778 -0.4971 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9905 -1.2413 -0.7716 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4213 -3.0923 -4.1386 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6056 -2.0585 -3.1793 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3815 -3.7964 -2.8374 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2237 -2.2904 -1.2667 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0363 -1.0175 2.5730 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4388 -1.2500 3.8721 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9568 0.4077 3.4539 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1526 -0.7138 4.0981 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6279 -2.5939 1.3012 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7341 0.0093 2.4546 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0610 -1.9220 3.0830 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3928 -0.6953 4.1574 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5072 -1.8433 4.4033 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2472 1.5276 3.1062 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2846 2.1379 -0.5893 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9009 0.1046 -3.9182 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4301 -0.3959 -3.1827 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0098 1.3712 -3.1930 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9578 3.3220 2.9351 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 8 13 1 0 4 14 1 0 3 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 21 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 31 32 1 0 29 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 37 38 1 0 34 39 1 0 39 40 2 0 10 5 1 0 23 16 1 0 30 26 1 0 36 28 1 0 1 41 1 0 2 42 1 0 2 43 1 0 3 44 1 1 4 45 1 1 6 46 1 0 7 47 1 0 10 48 1 0 12 49 1 0 12 50 1 0 12 51 1 0 13 52 1 0 14 53 1 0 19 54 1 0 19 55 1 0 19 56 1 0 20 57 1 0 22 58 1 0 25 59 1 0 25 60 1 0 25 61 1 0 26 62 1 1 30 63 1 1 31 64 1 0 31 65 1 0 32 66 1 0 33 67 1 0 35 68 1 0 38 69 1 0 38 70 1 0 38 71 1 0 39 72 1 0 M END

Standard InCHIKey	HSGQUCFRADTCMJ-WXYGLEJPSA-N
Standard InCHI	InChI=1S/C29H32O11/c1-35-21-9-16(5-6-20(21)33)26(34)25(14-32)39-29-23(37-3)10-17(11-24(29)38-4)27-19(13-31)18-7-15(12-30)8-22(36-2)28(18)40-27/h5-12,19,25-27,31-34H,13-14H2,1-4H3/t19-,25-,26+,27+/m1/s1
SMILES	OC[C@H]([C@H](c1ccc(c(c1)OC)O)O)Oc1c(OC)cc(cc1OC)[C@@H]1Oc2c([C@H]1CO)cc(cc2OC)C=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	556.19	Volume:	546.242 ? Van der Waals volume.
Dense:	1.018	LogP:	1.781 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.213 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.825 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	23.0
TPSA:	153.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.244	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.112	Fsp³:	0.345
MCE-18:	83.769 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.788	Fluc inhibitor:	0.289 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.05 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.552 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.234	Promiscuous compounds:	0.271

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.432	MDCK Permeability:	-5.077
Pgp-inhibitor:	0.679	Pgp-substrate:	0.036
PAMPA:	0.212 ? 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%):	0.038	30% Bioavailability (F30%):	0.044
50% Bioavailability (F50%):	0.807

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.109	MRP1:	0.416
Plasma Protein Binding (PPB):	78.305%	Volume Distribution (VD):	0.132
Fu:	23.825% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.808
BSEP inhibitor:	0.875

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.511	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.01	CYP2C9-substrate:	0.158
CYP2D6-inhibitor:	0.008	CYP2D6-substrate:	0.148
CYP3A4-inhibitor:	0.303	CYP3A4-substrate:	0.038
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.942
HLM stability:	0.0 ? 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):

5.978

Half-life (T1/2):

1.944

ADMET: Toxicity

hERG Blockers:	0.07	hERG Blockers (10um):	0.2
Human Hepatotoxicity (H-HT):	0.932	Drug-induced Liver Injury (DILI):	0.617
AMES Toxicity:	0.591	Rat Oral Acute Toxicity:	0.2
Maximum Recommended Daily Dose:	0.146	Skin Sensitization:	0.982
Carcinogencity:	0.343	Eye Corrosion:	0.0
Eye Irritation:	0.422	Respiratory Toxicity:	0.287
Drug-induced Neurotoxicity:	0.735	Ototoxicity:	0.798
Hematotoxicity:	0.391	Drug-induced Nephrotoxicity:	0.682
Genotoxicity:	0.501	RPMI-8226 Immunitoxicity:	0.283
A549 Cytotoxicity:	0.69	Hek293 Cytotoxicity:	0.411
BCF:	0.589 ? 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:	3.385 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.919 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.075 ? 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
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	stem	n.a.	PMID[21469695]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	skin-removed stems	Pingle Town, Sichuang Province, China	2008-AUG	PMID[21469695]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22690646]
NPO19192	Sinocalamus affinis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19192	Sinocalamus affinis	Species	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

Activity Type	# Activity
Inhibition	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.	Inhibition	<	30.0	%	PMID[21469695]

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 NPC43065 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	26746
0.1-0.2	20437
0.2-0.3	2392
0.3-0.4	196
0.4-0.5	52
0.5-0.6	19
0.6-0.7	5
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
0.76	Intermediate Similarity	NPC470769
0.7568	Intermediate Similarity	NPC260397
0.7403	Intermediate Similarity	NPC470828
0.7037	Intermediate Similarity	NPC470827
0.6818	Remote Similarity	NPC300757
0.6264	Remote Similarity	NPC485396
0.6264	Remote Similarity	NPC485394
0.6264	Remote Similarity	NPC485395
0.6154	Remote Similarity	NPC181615
0.5797	Remote Similarity	NPC9370
0.5797	Remote Similarity	NPC287495
0.56	Remote Similarity	NPC470098
0.56	Remote Similarity	NPC473266
0.5588	Remote Similarity	NPC310854
0.5417	Remote Similarity	NPC16208
0.5405	Remote Similarity	NPC267291
0.5405	Remote Similarity	NPC481839
0.5385	Remote Similarity	NPC470097
0.5366	Remote Similarity	NPC473236
0.5342	Remote Similarity	NPC7903
0.5342	Remote Similarity	NPC160991
0.5316	Remote Similarity	NPC470826
0.5132	Remote Similarity	NPC472961
0.5132	Remote Similarity	NPC472962
0.5067	Remote Similarity	NPC75695
0.5065	Remote Similarity	NPC284881
0.5065	Remote Similarity	NPC93433
0.5065	Remote Similarity	NPC474444

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC43065 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5067
0.1-0.2	4000
0.2-0.3	80
0.3-0.4	3
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