NPASS Compound

Natural Product: NPC238834

Natural Product ID	NPC238834
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Schizarin C
IUPAC Name	n.a.
Synonyms	Schizarin C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL476699
PubChem CID	10743985
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 6.6414 2.5168 0.5187 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3302 1.2198 0.8050 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3648 0.2527 1.4431 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1822 -0.0341 0.5477 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2883 -1.0130 1.2841 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0936 -1.3736 0.5090 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2032 -2.2208 -0.4438 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8116 -0.8819 0.6983 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7113 -1.2743 -0.0904 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3228 -1.9578 0.7407 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4394 -2.5060 1.9622 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1645 -3.0011 0.1980 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2914 -3.9128 -0.6971 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3960 -2.7356 -0.5802 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9331 -1.3920 -0.2621 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3899 -0.1060 -0.4162 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1504 0.3268 -1.0331 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1613 -0.1251 -0.8636 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1302 0.5311 -1.5252 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8149 1.6176 -2.3444 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5892 2.4626 -3.1244 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8017 3.6162 -3.4549 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5147 3.1142 -3.3479 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5189 2.0353 -2.4895 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5320 1.3781 -1.8245 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8710 1.6822 -1.9105 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0008 1.0613 -0.0356 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3053 2.2391 -0.2343 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4447 2.8036 0.7390 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2473 0.9278 0.5278 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8328 -0.3365 0.6984 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1580 -1.4685 0.2992 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0899 -0.4225 1.2702 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.6718 -1.6984 1.4384 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9053 2.0834 0.9213 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7701 2.7760 0.0179 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0032 2.4758 -0.3881 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4459 3.2868 0.3915 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9746 2.7901 1.3616 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1649 1.3632 1.5219 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7502 0.7350 -0.0896 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8594 -0.7345 1.6333 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9794 0.5988 2.4123 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5598 -0.4660 -0.3949 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5733 0.8654 0.3309 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9033 -1.9571 1.3825 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0941 -0.7154 2.3322 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0872 -2.0091 -0.8266 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9722 -1.1589 1.2022 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1066 -3.3256 1.6889 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2799 -2.8792 2.7165 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9469 -1.6243 2.4006 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4000 -3.7228 1.0708 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0828 -3.4239 -1.6663 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6261 -4.1546 -0.1420 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8944 -4.8502 -0.8881 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2292 -3.4541 -0.3486 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1787 -2.7617 -1.6836 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1658 0.1989 -1.4106 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0386 3.9509 -4.4834 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0020 4.4403 -2.7425 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5557 1.1616 -2.4253 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6531 2.3281 1.7276 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6664 3.8921 0.8793 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3761 2.6043 0.5301 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5878 -2.4745 0.4206 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8507 -2.2185 0.4816 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0170 -2.3545 2.0617 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6208 -1.5463 1.9967 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5042 2.5839 -1.0338 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8163 2.5124 0.2762 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6483 3.8593 0.2076 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 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 10 12 1 0 12 13 1 0 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 16 27 1 0 27 28 1 0 28 29 1 0 27 30 2 0 30 31 1 0 31 32 2 0 31 33 1 0 33 34 1 0 30 35 1 0 35 36 1 0 18 9 1 0 24 20 1 0 32 15 1 0 25 17 1 0 1 37 1 0 1 38 1 0 1 39 1 0 2 40 1 0 2 41 1 0 3 42 1 0 3 43 1 0 4 44 1 0 4 45 1 0 5 46 1 0 5 47 1 0 9 48 1 6 10 49 1 1 11 50 1 0 11 51 1 0 11 52 1 0 12 53 1 1 13 54 1 0 13 55 1 0 13 56 1 0 14 57 1 0 14 58 1 0 19 59 1 0 22 60 1 0 22 61 1 0 26 62 1 0 29 63 1 0 29 64 1 0 29 65 1 0 32 66 1 0 34 67 1 0 34 68 1 0 34 69 1 0 36 70 1 0 36 71 1 0 36 72 1 0 M END

Standard InCHIKey	XEIWTSUWNIHCLK-RKPUJPDHSA-N
Standard InCHI	InChI=1S/C28H36O8/c1-7-8-9-10-21(29)36-25-16(3)15(2)11-17-12-19(31-4)27(32-5)28(33-6)22(17)23-18(25)13-20-26(24(23)30)35-14-34-20/h12-13,15-16,25,30H,7-11,14H2,1-6H3/t15-,16-,25+/m1/s1
SMILES	CCCCCC(=O)O[C@H]1[C@H](C)[C@H](C)Cc2c(c3c1cc1OCOc1c3O)c(OC)c(c(c2)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	500.24	Volume:	510.485 ? Van der Waals volume.
Dense:	0.98	LogP:	5.37 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.09 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.418 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	23.0
TPSA:	92.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.359	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.921	Fsp³:	0.536
MCE-18:	84.047 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.871	Fluc inhibitor:	0.079 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.357 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.708 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.202	Promiscuous compounds:	0.477

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.963	MDCK Permeability:	-4.709
Pgp-inhibitor:	0.061	Pgp-substrate:	0.232
PAMPA:	0.183 ? 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%):	0.214	30% Bioavailability (F30%):	0.006
50% Bioavailability (F50%):	0.946

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.487	MRP1:	0.996
Plasma Protein Binding (PPB):	98.081%	Volume Distribution (VD):	-0.096
Fu:	1.76% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.504
OATP1B3 inhibitor:	0.629	BCRP inhibitor:	0.035
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.067	CYP1A2-substrate:	0.991
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.997
CYP2C9-inhibitor:	0.572	CYP2C9-substrate:	0.21
CYP2D6-inhibitor:	0.004	CYP2D6-substrate:	0.974
CYP3A4-inhibitor:	0.915	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.048	CYP2C8-inhibitor:	0.995
HLM stability:	0.552 ? 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):

4.317

Half-life (T1/2):

0.764

ADMET: Toxicity

hERG Blockers:	0.181	hERG Blockers (10um):	0.564
Human Hepatotoxicity (H-HT):	0.603	Drug-induced Liver Injury (DILI):	0.874
AMES Toxicity:	0.629	Rat Oral Acute Toxicity:	0.382
Maximum Recommended Daily Dose:	0.653	Skin Sensitization:	0.874
Carcinogencity:	0.889	Eye Corrosion:	0.005
Eye Irritation:	0.475	Respiratory Toxicity:	0.822
Drug-induced Neurotoxicity:	0.43	Ototoxicity:	0.545
Hematotoxicity:	0.747	Drug-induced Nephrotoxicity:	0.888
Genotoxicity:	0.019	RPMI-8226 Immunitoxicity:	0.315
A549 Cytotoxicity:	0.813	Hek293 Cytotoxicity:	0.462
BCF:	1.949 ? 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:	4.703 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.361 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.704 ? 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
NPO10144	Kadsura matsudai	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[11215493]
NPO10144	Kadsura matsudai	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11325232]
NPO10144	Kadsura matsudai	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10144	Kadsura matsudai	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10144	Kadsura matsudai	Species	Schisandraceae	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
Activity	2

Activity Type	# Activity
Organism	2

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
NPT963	Organism	Hepatitis B virus	Hepatitis B virus	Activity	<	25.0	%	PMID[25128665]

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 NPC238834 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	9151
0.1-0.2	38077
0.2-0.3	2433
0.3-0.4	85
0.4-0.5	84
0.5-0.6	15
0.6-0.7	6
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
0.8676	High Similarity	NPC475756
0.7917	Intermediate Similarity	NPC474606
0.7794	Intermediate Similarity	NPC121661
0.7286	Intermediate Similarity	NPC154971
0.7051	Intermediate Similarity	NPC311912
0.6438	Remote Similarity	NPC252286
0.6232	Remote Similarity	NPC184684
0.6232	Remote Similarity	NPC184641
0.6203	Remote Similarity	NPC476065
0.6111	Remote Similarity	NPC76415
0.6111	Remote Similarity	NPC218510
0.5867	Remote Similarity	NPC73467
0.5844	Remote Similarity	NPC471154
0.5658	Remote Similarity	NPC85141
0.5632	Remote Similarity	NPC230531
0.5616	Remote Similarity	NPC321958
0.5571	Remote Similarity	NPC865
0.5542	Remote Similarity	NPC63061
0.5529	Remote Similarity	NPC485504
0.5357	Remote Similarity	NPC475229
0.5342	Remote Similarity	NPC133934
0.5325	Remote Similarity	NPC316989
0.5169	Remote Similarity	NPC215400
0.5135	Remote Similarity	NPC318286
0.5128	Remote Similarity	NPC474393
0.5128	Remote Similarity	NPC474347

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC238834 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3696
0.1-0.2	5368
0.2-0.3	84
0.3-0.4	2
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