NPASS Compound

Natural Product: NPC485877

Natural Product ID	NPC485877
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	WZXDUFKPIPWSLK-GEBQIGAGSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	24970586
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001557] Bufanolides and derivatives

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 67 72 0 0 0 0 0 0 0 0999 V2000 5.3984 -2.4383 2.4743 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0262 -2.2963 1.9065 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2056 -3.2611 1.8949 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5846 -1.0977 1.3635 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3006 -0.9222 0.8189 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3117 -0.6060 -0.6400 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6538 -0.2582 -1.1104 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2218 -0.8210 -2.2463 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4862 -0.5064 -2.6942 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2156 0.4292 -1.9520 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3705 0.7134 -2.3654 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6763 0.9578 -0.8809 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4638 0.6537 -0.4545 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2668 0.4721 -0.8721 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0096 1.7088 -1.3739 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2959 0.1162 -1.9692 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9186 1.0026 -1.7860 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6039 0.4820 -0.5482 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7637 0.7861 0.6261 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2510 -0.1183 1.7700 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.7012 -0.5076 1.5697 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5171 0.5968 0.9568 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9486 0.1030 0.8702 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0622 -1.1423 0.0070 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2872 -0.9776 -1.2784 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9315 0.4804 -1.4611 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0108 1.0021 -0.4057 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0562 2.5231 -0.4712 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4123 -1.3409 -0.2878 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1314 0.4988 2.9960 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6948 0.7314 0.4448 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4775 0.0911 1.5191 C 0 0 2 0 0 0 0 0 0 0 0 0 1.5461 1.4326 1.3148 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1586 -2.2778 1.6758 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5065 -3.4579 2.8532 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5196 -1.7410 3.3189 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7747 -1.9171 0.9291 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9613 -1.4676 -1.2831 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6502 -1.5412 -2.8108 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9256 -0.9479 -3.5809 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1256 1.1417 0.4254 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3367 2.3715 -0.5744 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8187 1.4276 -2.1001 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3180 2.3373 -2.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7260 0.3670 -2.9671 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0075 -0.9403 -1.8910 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6460 2.0569 -1.5767 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5786 0.9931 -2.6747 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6804 -0.6229 -0.6580 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0300 1.8282 0.9766 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6730 -1.0863 1.7110 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7847 -1.4502 0.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1625 -0.7490 2.5498 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5158 1.4502 1.6486 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6628 0.8855 0.5955 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2189 -0.2283 1.9097 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7095 -2.0021 0.5773 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3988 -1.6064 -1.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9447 -1.2504 -2.1411 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5741 0.6139 -2.4811 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8927 1.0488 -1.3780 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6697 2.9842 0.4632 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5209 2.8785 -1.3741 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1318 2.7945 -0.6221 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7561 -0.4465 -0.5769 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8948 0.3052 3.6031 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0216 -0.2388 2.4646 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 6 14 1 0 14 15 1 6 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 1 24 29 1 0 20 30 1 0 19 31 1 0 31 32 1 0 32 33 1 0 32 5 1 0 13 7 2 0 31 14 1 0 27 18 1 0 31 33 1 1 27 22 1 0 1 34 1 0 1 35 1 0 1 36 1 0 5 37 1 6 6 38 1 6 8 39 1 0 9 40 1 0 13 41 1 0 15 42 1 0 15 43 1 0 15 44 1 0 16 45 1 0 16 46 1 0 17 47 1 0 17 48 1 0 18 49 1 6 19 50 1 1 20 51 1 1 21 52 1 0 21 53 1 0 22 54 1 1 23 55 1 0 23 56 1 0 24 57 1 1 25 58 1 0 25 59 1 0 26 60 1 0 26 61 1 0 28 62 1 0 28 63 1 0 28 64 1 0 29 65 1 0 30 66 1 0 32 67 1 1 M END

Standard InCHIKey	WZXDUFKPIPWSLK-GEBQIGAGSA-N
Standard InCHI	InChI=1S/C26H34O7/c1-13(27)32-22-20(14-4-5-19(30)31-12-14)25(3)9-7-17-21(26(25)23(22)33-26)18(29)11-15-10-16(28)6-8-24(15,17)2/h4-5,12,15-18,20-23,28-29H,6-11H2,1-3H3/t15-,16-,17-,18-,20-,21-,22+,23+,24-,25+,26+/m0/s1
SMILES	CC(=O)O[C@@H]1[C@H](c2ccc(=O)oc2)[C@@]2(C)CC[C@H]3[C@@H]([C@H](C[C@@H]4C[C@H](CC[C@]34C)O)O)[C@]32[C@@H]1O3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	458.23	Volume:	457.899 ? Van der Waals volume.
Dense:	1.001	LogP:	1.976 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.345 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.653 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	30.0
TPSA:	109.5 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.518	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.429	Fsp³:	0.769
MCE-18:	180.087 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.846	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.39 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.045	Promiscuous compounds:	0.652

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.428	MDCK Permeability:	-5.033
Pgp-inhibitor:	0.045	Pgp-substrate:	0.053
PAMPA:	0.887 ? 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):	0.005
20% Bioavailability (F20%):	0.847	30% Bioavailability (F30%):	0.776
50% Bioavailability (F50%):	0.915

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.959
Plasma Protein Binding (PPB):	62.936%	Volume Distribution (VD):	-0.395
Fu:	37.824% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.002
BSEP inhibitor:	0.946

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.003
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.747
HLM stability:	0.357 ? 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):

9.826

Half-life (T1/2):

1.977

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.066
Human Hepatotoxicity (H-HT):	0.473	Drug-induced Liver Injury (DILI):	0.334
AMES Toxicity:	0.512	Rat Oral Acute Toxicity:	0.33
Maximum Recommended Daily Dose:	0.877	Skin Sensitization:	0.84
Carcinogencity:	0.851	Eye Corrosion:	0.005
Eye Irritation:	0.589	Respiratory Toxicity:	0.317
Drug-induced Neurotoxicity:	0.063	Ototoxicity:	0.422
Hematotoxicity:	0.303	Drug-induced Nephrotoxicity:	0.832
Genotoxicity:	0.992	RPMI-8226 Immunitoxicity:	0.168
A549 Cytotoxicity:	0.107	Hek293 Cytotoxicity:	0.416
BCF:	0.46 ? 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:	3.162 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.727 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.869 ? 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
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18558746]
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20112	Syncephalastrum racemosum	Species	Syncephalastraceae	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	1

Activity Type	# Activity
Cell line	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
NPT181	Cell line	Bel-7402	Homo sapiens	IC50	=	540.0	nM	PMID[18558746]

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 NPC485877 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	10354
0.1-0.2	37125
0.2-0.3	2285
0.3-0.4	61
0.4-0.5	15
0.5-0.6	12
0.6-0.7	2
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
0.8133	Intermediate Similarity	NPC157380
0.7436	Intermediate Similarity	NPC16701
0.7037	Intermediate Similarity	NPC35171
0.6429	Remote Similarity	NPC213761
0.6071	Remote Similarity	NPC75389
0.5714	Remote Similarity	NPC185287
0.5714	Remote Similarity	NPC43063
0.5714	Remote Similarity	NPC79298
0.5667	Remote Similarity	NPC485878
0.5393	Remote Similarity	NPC221414
0.5312	Remote Similarity	NPC312481
0.5172	Remote Similarity	NPC171126
0.5169	Remote Similarity	NPC159499
0.5059	Remote Similarity	NPC189863
0.5056	Remote Similarity	NPC103491
0.5056	Remote Similarity	NPC278681
0.5055	Remote Similarity	NPC485880

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC485877 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3364
0.1-0.2	5710
0.2-0.3	66
0.3-0.4	10
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