NPASS Compound

Natural Product: NPC570668

Natural Product ID	NPC570668
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(hydroxymethyl)-1-methoxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-anthracene-9,10-dione
IUPAC Name	2-(hydroxymethyl)-1-methoxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-anthracene-9,10-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic 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 54 57 0 0 0 0 0 0 0 0999 V2000 3.2844 -3.8631 -0.3542 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9301 -2.8784 -1.2998 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1028 -1.8274 -0.9220 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7411 -1.8901 -1.0183 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0745 -3.1053 -1.5372 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0833 -4.0674 -0.5307 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0966 -0.8418 -0.6423 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4686 -0.9593 -0.7611 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4473 -0.0508 -0.4485 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.3416 -0.5158 0.5417 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9876 0.6086 1.0454 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7966 0.1399 2.2387 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7141 -0.8174 1.8311 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8815 1.2762 0.0155 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4202 2.4037 0.6283 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0361 1.6279 -1.1807 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7385 2.2190 -2.2006 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3310 0.3449 -1.6123 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6466 0.4986 -2.7928 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5122 0.2916 -0.1566 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8911 0.4167 -0.0345 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6652 -0.6543 -0.4230 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0973 -0.5518 -0.3100 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8176 -1.5212 -0.6616 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6828 0.6887 0.2151 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0695 0.7941 0.3273 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6938 1.9266 0.8113 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8887 2.9896 1.1954 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5161 2.9124 1.0952 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9010 1.7599 0.6037 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4568 1.6578 0.4899 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7138 2.6106 0.8330 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3489 -4.1902 -0.4258 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1409 -3.5064 0.6885 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7032 -4.8082 -0.4731 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6727 -3.4956 -2.3931 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9794 -2.9313 -1.8073 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5912 -4.7622 -0.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0226 0.8779 -0.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1935 1.3007 1.4108 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0772 -0.3825 2.9178 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2463 0.9607 2.7978 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3982 -1.1919 0.9763 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6415 0.5549 -0.2948 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1225 2.7600 0.0064 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2060 2.2896 -0.7961 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6637 3.2186 -2.0801 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1251 -0.4277 -1.7096 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4442 1.4468 -2.9451 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0653 1.1525 0.1583 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6338 -0.0785 0.0069 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7712 1.9636 0.8806 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3762 3.8795 1.5755 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9139 3.7473 1.3984 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 1 0 4 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 11 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 7 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 22 3 1 0 30 25 1 0 18 9 1 0 31 21 1 0 1 33 1 0 1 34 1 0 1 35 1 0 5 36 1 0 5 37 1 0 6 38 1 0 9 39 1 1 11 40 1 1 12 41 1 0 12 42 1 0 13 43 1 0 14 44 1 6 15 45 1 0 16 46 1 1 17 47 1 0 18 48 1 6 19 49 1 0 20 50 1 0 26 51 1 0 27 52 1 0 28 53 1 0 29 54 1 0 M END

Standard InCHIKey	SYWNPFLHKSCNDM-MNKKRNMXSA-N
Standard InCHI	InChI=1S/C22H22O10/c1-30-21-12(7-23)13(31-22-20(29)19(28)18(27)14(8-24)32-22)6-11-15(21)17(26)10-5-3-2-4-9(10)16(11)25/h2-6,14,18-20,22-24,27-29H,7-8H2,1H3/t14-,18-,19+,20-,22-/m1/s1
SMILES	COC1=C(CO)C(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)=CC2=C1C(=O)C1=CC=CC=C1C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	446.12	Volume:	421.653 ? Van der Waals volume.
Dense:	1.058	LogP:	1.644 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.916 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.628 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	162.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.333	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.885	Fsp³:	0.364
MCE-18:	86.667 ? 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:	1
Colloidal aggregators:	0.355	Fluc inhibitor:	0.172 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.332 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.619 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.104	Promiscuous compounds:	0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.79	MDCK Permeability:	-5.082
Pgp-inhibitor:	0.027	Pgp-substrate:	0.028
PAMPA:	0.957 ? 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):	0.958
20% Bioavailability (F20%):	0.032	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018	MRP1:	0.049
Plasma Protein Binding (PPB):	84.835%	Volume Distribution (VD):	-0.066
Fu:	15.472% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.022
BSEP inhibitor:	0.007

ADMET: Metabolism

CYP1A2-inhibitor:	0.007	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.017	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.757
HLM stability:	0.103 ? 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):

2.756

Half-life (T1/2):

3.077

ADMET: Toxicity

hERG Blockers:	0.021	hERG Blockers (10um):	0.134
Human Hepatotoxicity (H-HT):	0.843	Drug-induced Liver Injury (DILI):	0.951
AMES Toxicity:	0.969	Rat Oral Acute Toxicity:	0.02
Maximum Recommended Daily Dose:	0.031	Skin Sensitization:	0.995
Carcinogencity:	0.78	Eye Corrosion:	0.0
Eye Irritation:	0.156	Respiratory Toxicity:	0.011
Drug-induced Neurotoxicity:	0.087	Ototoxicity:	0.93
Hematotoxicity:	0.829	Drug-induced Nephrotoxicity:	0.713
Genotoxicity:	0.852	RPMI-8226 Immunitoxicity:	0.163
A549 Cytotoxicity:	0.433	Hek293 Cytotoxicity:	0.352
BCF:	0.575 ? 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:	3.198 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.843 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.883 ? 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
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	leaf	n.a.	PMID[11348221]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	fruit	n.a.	n.a.	PMID[15844957]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	fruits	n.a.	n.a.	PMID[16378361]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	fruits	Tahiti	n.a.	PMID[17378609]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[17480098]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	roots	n.a.	n.a.	PMID[18076142]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24224843]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27196335]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[32083868]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36014413]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO45093	Lasianthus acuminatissimus MERR.	Genus	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4323	Morinda citrifolia	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4323	Morinda citrifolia	Species	Rubiaceae	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 NPC570668 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	14480
0.1-0.2	31111
0.2-0.3	3397
0.3-0.4	653
0.4-0.5	189
0.5-0.6	19
0.6-0.7	3
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
0.6769	Remote Similarity	NPC610808
0.6154	Remote Similarity	NPC222455
0.6143	Remote Similarity	NPC605700
0.5972	Remote Similarity	NPC212099
0.5902	Remote Similarity	NPC226712
0.5833	Remote Similarity	NPC101116
0.5753	Remote Similarity	NPC606202
0.5738	Remote Similarity	NPC299144
0.5694	Remote Similarity	NPC146837
0.5645	Remote Similarity	NPC608788
0.5541	Remote Similarity	NPC76128
0.5493	Remote Similarity	NPC146803
0.5479	Remote Similarity	NPC278329
0.5479	Remote Similarity	NPC30432
0.5469	Remote Similarity	NPC166040
0.5333	Remote Similarity	NPC199357
0.5303	Remote Similarity	NPC218685
0.5246	Remote Similarity	NPC269242
0.5077	Remote Similarity	NPC69513
0.5068	Remote Similarity	NPC600107
0.5067	Remote Similarity	NPC5029
0.5065	Remote Similarity	NPC217950

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC570668 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3532
0.1-0.2	5429
0.2-0.3	179
0.3-0.4	7
0.4-0.5	2
0.5-0.6	1
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
0.5902	Remote Similarity	NPD1091	Pre-clinical

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