NPASS Compound

Natural Product: NPC307178

Natural Product ID	NPC307178
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RNQBLQALVMHBKH-JXALSKIBSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12991583
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001586] Biflavonoids and polyflavonoids

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 62 67 0 0 0 0 0 0 0 0999 V2000 -1.9725 1.5942 2.2884 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0875 2.7040 3.1173 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8342 3.7788 2.7111 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4510 3.7391 1.4998 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3279 2.6358 0.6920 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5738 1.5042 1.0583 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5033 0.4125 0.1212 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4890 0.6254 -1.0203 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1563 0.8198 -0.4551 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9317 1.2030 -1.3872 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9107 1.2004 -2.6172 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1689 1.6359 -0.7105 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1767 2.2729 -1.4296 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3287 2.6778 -0.7910 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4498 2.4343 0.5683 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4446 1.8034 1.2638 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2652 1.3826 0.6367 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2507 0.7386 1.3735 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4094 -0.1208 0.5176 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3693 -1.1567 0.0701 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2836 -1.6689 1.0188 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2135 -2.6250 0.7397 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2702 -3.1213 -0.5294 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4044 -2.6539 -1.4778 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4472 -1.6679 -1.1850 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2052 -4.0952 -0.8459 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6170 2.8516 1.1849 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9823 2.4845 -2.8014 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7171 -0.3761 -2.0444 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5920 -0.1550 -3.2563 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1129 -1.7084 -1.6286 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1206 -2.7765 -2.5354 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5003 -4.0206 -2.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8793 -4.2700 -0.8027 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8713 -3.2203 0.0868 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4872 -1.9346 -0.3259 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4927 -0.8944 0.6103 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2648 -5.5384 -0.3697 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7351 -2.4950 -3.8350 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9366 4.8923 3.5672 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3891 0.7581 2.6290 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6020 2.7465 4.0813 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0390 4.5973 1.1915 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8316 2.6516 -0.2515 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5137 0.4444 -0.4577 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8265 1.6178 -1.4561 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2906 1.8131 0.1461 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0879 3.1686 -1.3822 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5624 1.6256 2.3193 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2982 -0.6594 1.1779 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2377 -1.2729 2.0302 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8761 -2.9573 1.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4293 -3.0359 -2.5040 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8038 -1.3671 -2.0074 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5271 -4.2128 -1.7853 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7854 3.8409 1.3369 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3059 3.2149 -3.0257 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5060 -4.8537 -2.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1636 -3.3791 1.1201 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2413 -5.7789 -0.5189 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1166 -3.0935 -4.3821 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8214 5.2397 3.8532 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 23 26 1 0 15 27 1 0 13 28 1 0 8 29 1 0 29 30 2 0 29 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 35 36 2 0 36 37 1 0 34 38 1 0 32 39 1 0 3 40 1 0 6 1 1 0 37 7 1 0 19 9 1 0 25 20 1 0 36 31 1 0 17 12 1 0 1 41 1 0 2 42 1 0 4 43 1 0 5 44 1 0 7 45 1 6 8 46 1 6 9 47 1 1 14 48 1 0 16 49 1 0 19 50 1 1 21 51 1 0 22 52 1 0 24 53 1 0 25 54 1 0 26 55 1 0 27 56 1 0 28 57 1 0 33 58 1 0 35 59 1 0 38 60 1 0 39 61 1 0 40 62 1 0 M END

Standard InCHIKey	RNQBLQALVMHBKH-JXALSKIBSA-N
Standard InCHI	InChI=1S/C30H22O10/c31-15-5-1-13(2-6-15)29-25(27(37)23-19(35)9-17(33)11-21(23)39-29)26-28(38)24-20(36)10-18(34)12-22(24)40-30(26)14-3-7-16(32)8-4-14/h1-12,25-26,29-36H/t25-,26+,29-,30+
SMILES	c1cc(ccc1[C@H]1[C@@H]([C@@H]2C(=O)c3c(cc(cc3O[C@@H]2c2ccc(cc2)O)O)O)C(=O)c2c(cc(cc2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	542.12	Volume:	527.089 ? Van der Waals volume.
Dense:	1.029	LogP:	3.181 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.95 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.864 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	36.0
TPSA:	173.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	6.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.216	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.022	Fsp³:	0.133
MCE-18:	116.471 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.985	Fluc inhibitor:	0.648 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.066 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.702 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.606	Promiscuous compounds:	0.291

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.546	MDCK Permeability:	-4.828
Pgp-inhibitor:	0.093	Pgp-substrate:	0.128
PAMPA:	0.03 ? 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%):	0.064	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.858
Plasma Protein Binding (PPB):	95.198%	Volume Distribution (VD):	-0.097
Fu:	7.868% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.995
BSEP inhibitor:	0.831

ADMET: Metabolism

CYP1A2-inhibitor:	0.991	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.016	CYP2C19-substrate:	0.565
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.993	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.536
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.995
HLM stability:	0.76 ? 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):

5.966

Half-life (T1/2):

2.04

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.608
Human Hepatotoxicity (H-HT):	0.604	Drug-induced Liver Injury (DILI):	0.734
AMES Toxicity:	0.678	Rat Oral Acute Toxicity:	0.482
Maximum Recommended Daily Dose:	0.815	Skin Sensitization:	0.954
Carcinogencity:	0.384	Eye Corrosion:	0.0
Eye Irritation:	0.966	Respiratory Toxicity:	0.782
Drug-induced Neurotoxicity:	0.072	Ototoxicity:	0.488
Hematotoxicity:	0.072	Drug-induced Nephrotoxicity:	0.304
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.232
A549 Cytotoxicity:	0.915	Hek293 Cytotoxicity:	0.994
BCF:	1.169 ? 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:	4.003 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.598 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.226 ? 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
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	PMID[15997133]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	PMID[16141313]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	callus	n.a.	PMID[22368856]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23611151]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	roots	n.a.	n.a.	PMID[24931277]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26562066]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34770847]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	root	n.a.	Database[Article]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7067	Stellera chamaejasme	Species	Thymelaeaceae	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 NPC307178 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	24225
0.1-0.2	21300
0.2-0.3	3469
0.3-0.4	701
0.4-0.5	122
0.5-0.6	24
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC201227
1.0	High Similarity	NPC258474
0.8542	High Similarity	NPC484335
0.8039	Intermediate Similarity	NPC271741
0.7872	Intermediate Similarity	NPC287789
0.7292	Intermediate Similarity	NPC484336
0.7292	Intermediate Similarity	NPC484337
0.6863	Remote Similarity	NPC602118
0.6809	Remote Similarity	NPC603336
0.6481	Remote Similarity	NPC600886
0.64	Remote Similarity	NPC32441
0.64	Remote Similarity	NPC79943
0.5962	Remote Similarity	NPC62290
0.5962	Remote Similarity	NPC142731
0.5962	Remote Similarity	NPC326506
0.5517	Remote Similarity	NPC604757
0.5472	Remote Similarity	NPC295261
0.5472	Remote Similarity	NPC296490
0.5455	Remote Similarity	NPC321011
0.5455	Remote Similarity	NPC294852
0.5455	Remote Similarity	NPC188679
0.5319	Remote Similarity	NPC212379
0.5185	Remote Similarity	NPC243083
0.5185	Remote Similarity	NPC13768
0.5185	Remote Similarity	NPC129132
0.5185	Remote Similarity	NPC287246
0.5179	Remote Similarity	NPC118813
0.5091	Remote Similarity	NPC279417
0.5091	Remote Similarity	NPC49130
0.5088	Remote Similarity	NPC36835
0.5088	Remote Similarity	NPC246162
0.5088	Remote Similarity	NPC9743
0.5088	Remote Similarity	NPC260491
0.5088	Remote Similarity	NPC61506
0.5088	Remote Similarity	NPC240476
0.5085	Remote Similarity	NPC236637

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC307178 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4632
0.1-0.2	4397
0.2-0.3	107
0.3-0.4	7
0.4-0.5	5
0.5-0.6	1
0.6-0.7	1
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
0.64	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5185	Remote Similarity	NPD1550	Phase 2

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