NPASS Compound

Natural Product: NPC3855

Natural Product ID	NPC3855
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	BDRRAMWDUCXAKG-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	17203
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000134] Phenols [CHEMONTID:0000190] Methoxyphenols

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 24 24 0 0 0 0 0 0 0 0999 V2000 -2.3602 1.9016 0.0531 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0103 0.6445 -0.7126 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8986 -0.0709 -0.0495 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1219 -0.9025 1.0287 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0572 -1.5540 1.6220 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2387 -1.4140 1.1851 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4465 -0.5672 0.0912 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3902 0.0886 -0.5091 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7561 -0.4401 -0.3323 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0431 0.3903 -1.4222 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2695 -2.0801 1.8034 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1049 -0.1657 -0.9321 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3517 1.7094 0.5369 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4344 2.7902 -0.6087 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6036 2.1146 0.8473 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6614 0.9897 -1.7268 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1466 -1.0072 1.3666 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2977 -2.1909 2.4619 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5801 0.7363 -1.3522 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1568 0.5492 -1.4199 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8068 -0.0866 -2.4088 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5228 1.3577 -1.3944 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7933 -1.6747 2.5756 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9555 -1.1178 -0.7034 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 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 6 11 1 0 2 12 1 0 8 3 1 0 1 13 1 0 1 14 1 0 1 15 1 0 2 16 1 0 4 17 1 0 5 18 1 0 8 19 1 0 10 20 1 0 10 21 1 0 10 22 1 0 11 23 1 0 12 24 1 0 M END

Standard InCHIKey	BDRRAMWDUCXAKG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H12O3/c1-6(10)7-3-4-8(11)9(5-7)12-2/h3-6,10-11H,1-2H3
SMILES	CC(c1ccc(c(c1)OC)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	168.08	Volume:	174.125 ? Van der Waals volume.
Dense:	0.965	LogP:	0.544 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.93 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.821 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	6.0
TPSA:	49.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	2.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.702	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.25	Fsp³:	0.333
MCE-18:	14.0 ? 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:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.162	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.018 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.047 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.837	Promiscuous compounds:	0.627

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.013	MDCK Permeability:	-4.765
Pgp-inhibitor:	0.012	Pgp-substrate:	0.288
PAMPA:	0.537 ? 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):	0.148
20% Bioavailability (F20%):	0.554	30% Bioavailability (F30%):	0.7
50% Bioavailability (F50%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.051	MRP1:	0.817
Plasma Protein Binding (PPB):	42.701%	Volume Distribution (VD):	0.141
Fu:	53.665% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.944
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.354
BSEP inhibitor:	0.071

ADMET: Metabolism

CYP1A2-inhibitor:	0.17	CYP1A2-substrate:	0.052
CYP2C19-inhibitor:	0.339	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.045	CYP2C9-substrate:	0.009
CYP2D6-inhibitor:	0.071	CYP2D6-substrate:	0.048
CYP3A4-inhibitor:	0.023	CYP3A4-substrate:	0.253
CYP2B6-substrate:	0.055	CYP2C8-inhibitor:	0.915
HLM stability:	0.182 ? 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):

6.641

Half-life (T1/2):

1.808

ADMET: Toxicity

hERG Blockers:	0.085	hERG Blockers (10um):	0.561
Human Hepatotoxicity (H-HT):	0.332	Drug-induced Liver Injury (DILI):	0.097
AMES Toxicity:	0.374	Rat Oral Acute Toxicity:	0.232
Maximum Recommended Daily Dose:	0.228	Skin Sensitization:	0.293
Carcinogencity:	0.632	Eye Corrosion:	0.718
Eye Irritation:	0.985	Respiratory Toxicity:	0.537
Drug-induced Neurotoxicity:	0.373	Ototoxicity:	0.417
Hematotoxicity:	0.225	Drug-induced Nephrotoxicity:	0.268
Genotoxicity:	0.086	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.072	Hek293 Cytotoxicity:	0.137
BCF:	0.461 ? 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:	2.467 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.527 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	2.855 ? 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
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	rhizomes	n.a.	n.a.	PMID[11000020]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[21401114]
NPO29008	Coptis teeta	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22622	Coptis deltoidea	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22622	Coptis deltoidea	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22622	Coptis deltoidea	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16145	Apocynum venetum	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO22622	Coptis deltoidea	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29008	Coptis teeta	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5649	Coptis chinensis	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO29008	Coptis teeta	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13757	Coptis japonica	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22622	Coptis deltoidea	Species	Ranunculaceae	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 NPC3855 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	22245
0.1-0.2	20229
0.2-0.3	6416
0.3-0.4	686
0.4-0.5	207
0.5-0.6	59
0.6-0.7	9
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
0.7879	Intermediate Similarity	NPC181969
0.7576	Intermediate Similarity	NPC320987
0.7353	Intermediate Similarity	NPC326599
0.7353	Intermediate Similarity	NPC329595
0.7027	Intermediate Similarity	NPC195292
0.6944	Remote Similarity	NPC35071
0.6944	Remote Similarity	NPC177475
0.6944	Remote Similarity	NPC148615
0.6944	Remote Similarity	NPC476343
0.641	Remote Similarity	NPC165045
0.641	Remote Similarity	NPC118533
0.625	Remote Similarity	NPC7097
0.6176	Remote Similarity	NPC156840
0.6	Remote Similarity	NPC32163
0.5854	Remote Similarity	NPC476968
0.5714	Remote Similarity	NPC246358
0.5714	Remote Similarity	NPC203719
0.5714	Remote Similarity	NPC293619
0.5676	Remote Similarity	NPC160380
0.5676	Remote Similarity	NPC38996
0.5676	Remote Similarity	NPC8547
0.5676	Remote Similarity	NPC221049
0.5676	Remote Similarity	NPC36108
0.5676	Remote Similarity	NPC140359
0.5676	Remote Similarity	NPC233731
0.5676	Remote Similarity	NPC610203
0.5625	Remote Similarity	NPC203831
0.5556	Remote Similarity	NPC470990
0.5556	Remote Similarity	NPC309203
0.5556	Remote Similarity	NPC604189
0.5526	Remote Similarity	NPC165133
0.5526	Remote Similarity	NPC242885
0.5526	Remote Similarity	NPC16651
0.5526	Remote Similarity	NPC139519
0.5526	Remote Similarity	NPC95614
0.5526	Remote Similarity	NPC471693
0.5526	Remote Similarity	NPC232316
0.5435	Remote Similarity	NPC310854
0.5417	Remote Similarity	NPC480703
0.5405	Remote Similarity	NPC257124
0.5385	Remote Similarity	NPC255675
0.5366	Remote Similarity	NPC480479
0.5294	Remote Similarity	NPC291101
0.5294	Remote Similarity	NPC266197
0.5263	Remote Similarity	NPC159418
0.525	Remote Similarity	NPC78918
0.525	Remote Similarity	NPC57490
0.525	Remote Similarity	NPC85488
0.525	Remote Similarity	NPC139617
0.5208	Remote Similarity	NPC92164
0.52	Remote Similarity	NPC16208
0.52	Remote Similarity	NPC58607
0.52	Remote Similarity	NPC191037
0.52	Remote Similarity	NPC178284
0.5128	Remote Similarity	NPC193544
0.5122	Remote Similarity	NPC129889
0.5122	Remote Similarity	NPC282703
0.5122	Remote Similarity	NPC184733
0.5122	Remote Similarity	NPC128208
0.5122	Remote Similarity	NPC129570
0.5122	Remote Similarity	NPC50763
0.5122	Remote Similarity	NPC299406
0.5122	Remote Similarity	NPC307006
0.5122	Remote Similarity	NPC63238
0.5122	Remote Similarity	NPC325625
0.5122	Remote Similarity	NPC602603
0.5122	Remote Similarity	NPC606519
0.5116	Remote Similarity	NPC487676
0.5102	Remote Similarity	NPC9370
0.5102	Remote Similarity	NPC475875
0.5102	Remote Similarity	NPC287495
0.5098	Remote Similarity	NPC7903
0.5098	Remote Similarity	NPC160991

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC3855 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3677
0.1-0.2	5020
0.2-0.3	414
0.3-0.4	32
0.4-0.5	5
0.5-0.6	2
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
0.5405	Remote Similarity	NPD228	Phase 0
0.525	Remote Similarity	NPD824	Phase 4

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