NPASS Compound

Natural Product: NPC548600

Natural Product ID	NPC548600
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Gyrocarpusine
IUPAC Name	(1~{R},14~{R})-6,21,25-trimethoxy-15,30-dimethyl-8,23-dioxa-15,30-diazaheptacyclo[22.6.2.2^{9,12}.1^{3,7}.1^{14,18}.0^{27,31}.0^{22,33}]hexatriaconta-3,5,7(36),9,11,18(33),19,21,24(32),25,27(31),34-dodecaen-20-ol
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 85 91 0 0 0 0 0 0 0 0999 V2000 7.0558 2.7676 0.9436 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6597 2.9364 0.8299 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9222 1.9315 0.1748 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5565 0.8126 -0.3403 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8252 -0.1715 -0.9830 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4555 -0.0750 -1.1321 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8539 1.0374 -0.6163 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5663 2.0137 0.0198 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8939 3.1220 0.5247 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5054 3.1636 0.4655 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9153 3.4668 -0.7315 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4464 3.5156 -0.8283 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2176 3.2604 0.2757 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6299 2.9556 1.4796 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7459 2.9022 1.5946 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6887 3.3334 0.1229 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3968 2.0441 0.4519 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4246 1.0688 -0.6563 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1889 1.3200 -1.7519 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2576 0.4278 -2.8326 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5108 -0.7224 -2.7312 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5010 -1.6847 -3.7475 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7249 -1.0021 -1.6251 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9828 -2.1998 -1.5801 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5510 -3.3985 -1.0982 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6898 -0.0937 -0.5889 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9019 -0.3852 0.5084 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8874 -1.3036 0.6162 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1998 -1.3085 -0.2191 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2094 -2.2400 -0.0922 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0939 -3.1901 0.9200 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0191 -3.1955 1.7556 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9840 -2.2677 1.6287 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0942 -2.2694 2.4889 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1204 -3.2718 3.4844 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2019 -4.1782 1.0135 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4655 -3.3042 1.0296 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6170 -2.7509 -0.2842 N 0 0 0 0 0 0 0 0 0 0 0 0 4.3549 -3.7097 -1.0876 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4039 -2.3203 -0.9336 C 0 0 2 0 0 0 0 0 0 0 0 0 2.6681 -1.1065 -1.7978 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9916 2.5703 -1.8083 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2814 3.2011 -0.4931 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8241 2.4206 0.6051 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.0866 2.9831 1.8896 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5438 2.7194 -0.0716 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5460 3.5783 1.4857 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3331 1.8126 1.4408 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6295 0.7585 -0.2119 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3902 -1.0139 -1.3578 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7890 1.1664 -0.7084 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5287 3.6692 -1.6066 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8990 3.7597 -1.7945 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2161 2.7527 2.3551 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2277 2.6681 2.5176 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0759 4.0808 0.8809 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9419 3.7331 -0.8578 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0245 1.6420 1.3918 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8663 0.6313 -3.7031 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3526 -2.1269 -4.0017 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2739 -3.1216 -0.3006 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7371 -4.0161 -0.6903 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1337 -3.8897 -1.8943 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2657 -0.5764 -0.9984 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0145 -3.9718 2.5363 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0057 -4.2784 2.9889 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2676 -3.1657 4.2054 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0429 -3.2258 4.0874 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1875 -4.6959 1.9966 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2242 -4.8668 0.1557 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3463 -3.8970 1.2846 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2771 -2.5279 1.8163 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2873 -3.9816 -0.5530 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7048 -3.2308 -2.0482 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7250 -4.6021 -1.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1763 -3.1536 -1.6733 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7521 -0.7714 -2.2453 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3322 -1.5026 -2.6337 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5446 3.2940 -2.5538 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0025 2.3497 -2.2782 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3839 3.3660 -0.3252 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8454 4.2402 -0.4079 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1003 4.0883 1.8439 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0497 2.5605 2.2660 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2950 2.6404 2.5849 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 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 13 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 21 23 1 0 23 24 1 0 24 25 1 0 23 26 2 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 31 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 38 40 1 0 40 41 1 0 19 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 8 3 1 0 15 10 1 0 44 17 1 0 41 6 1 0 26 18 1 0 33 28 1 0 40 30 1 0 1 46 1 0 1 47 1 0 1 48 1 0 4 49 1 0 5 50 1 0 7 51 1 0 11 52 1 0 12 53 1 0 14 54 1 0 15 55 1 0 16 56 1 0 16 57 1 0 17 58 1 1 20 59 1 0 22 60 1 0 25 61 1 0 25 62 1 0 25 63 1 0 29 64 1 0 32 65 1 0 35 66 1 0 35 67 1 0 35 68 1 0 36 69 1 0 36 70 1 0 37 71 1 0 37 72 1 0 39 73 1 0 39 74 1 0 39 75 1 0 40 76 1 6 41 77 1 0 41 78 1 0 42 79 1 0 42 80 1 0 43 81 1 0 43 82 1 0 45 83 1 0 45 84 1 0 45 85 1 0 M END

Standard InCHIKey	VXPVPAHQYCJDTP-FQLXRVMXSA-N
Standard InCHI	InChI=1S/C37H40N2O6/c1-38-14-12-24-20-32(42-4)34-21-27(24)28(38)17-23-8-11-31(41-3)33(18-23)44-26-9-6-22(7-10-26)16-29-35-25(13-15-39(29)2)19-30(40)36(43-5)37(35)45-34/h6-11,18-21,28-29,40H,12-17H2,1-5H3/t28-,29-/m1/s1
SMILES	COC1=CC=C2C=C1OC1=CC=C(C=C1)C[C@@H]1C3=C(C=C(O)C(OC)=C3OC3=CC4=C(C=C3OC)CCN(C)[C@@H]4C2)CCN1C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	608.29	Volume:	631.71 ? Van der Waals volume.
Dense:	0.963	LogP:	3.325 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.971 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.079 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	42.0
TPSA:	72.86 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	1.0	Rings:	8.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.271	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.778	Fsp³:	0.351
MCE-18:	129.48 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.998	Fluc inhibitor:	0.026 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.765 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.963 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.185

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.865	MDCK Permeability:	-4.791
Pgp-inhibitor:	0.15	Pgp-substrate:	0.967
PAMPA:	0.004 ? 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):	0.001
20% Bioavailability (F20%):	0.878	30% Bioavailability (F30%):	0.903
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.792	MRP1:	0.986
Plasma Protein Binding (PPB):	73.136%	Volume Distribution (VD):	-0.144
Fu:	28.268% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.942
OATP1B3 inhibitor:	0.967	BCRP inhibitor:	0.894
BSEP inhibitor:	0.995

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.995	CYP2C9-substrate:	0.041
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.102
CYP2B6-substrate:	0.717	CYP2C8-inhibitor:	0.021
HLM stability:	0.031 ? 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):

7.871

Half-life (T1/2):

2.405

ADMET: Toxicity

hERG Blockers:	0.865	hERG Blockers (10um):	0.845
Human Hepatotoxicity (H-HT):	0.559	Drug-induced Liver Injury (DILI):	0.011
AMES Toxicity:	0.636	Rat Oral Acute Toxicity:	0.817
Maximum Recommended Daily Dose:	0.983	Skin Sensitization:	0.578
Carcinogencity:	0.757	Eye Corrosion:	0.0
Eye Irritation:	0.002	Respiratory Toxicity:	0.932
Drug-induced Neurotoxicity:	0.889	Ototoxicity:	0.291
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.367
Genotoxicity:	0.868	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.314	Hek293 Cytotoxicity:	0.622
BCF:	1.921 ? 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:	4.53 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.717 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.129 ? 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
NPO53338	Gyrocarpus americanus	Species	Hernandiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC548600 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	28593
0.1-0.2	19607
0.2-0.3	1388
0.3-0.4	125
0.4-0.5	31
0.5-0.6	48
0.6-0.7	32
0.7-0.8	3
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC311973
0.942	High Similarity	NPC239824
0.8243	Intermediate Similarity	NPC254441
0.7887	Intermediate Similarity	NPC76682
0.7887	Intermediate Similarity	NPC10908
0.7887	Intermediate Similarity	NPC63646
0.7887	Intermediate Similarity	NPC317145
0.7887	Intermediate Similarity	NPC198498
0.7887	Intermediate Similarity	NPC115284
0.7838	Intermediate Similarity	NPC290582
0.7838	Intermediate Similarity	NPC217748
0.7838	Intermediate Similarity	NPC182052
0.7838	Intermediate Similarity	NPC271013
0.7838	Intermediate Similarity	NPC42663
0.7838	Intermediate Similarity	NPC15414
0.7763	Intermediate Similarity	NPC116465
0.7733	Intermediate Similarity	NPC279228
0.7534	Intermediate Similarity	NPC276890
0.7432	Intermediate Similarity	NPC603603
0.7368	Intermediate Similarity	NPC73492
0.7368	Intermediate Similarity	NPC299990
0.7333	Intermediate Similarity	NPC12424
0.7333	Intermediate Similarity	NPC129518
0.7333	Intermediate Similarity	NPC251580
0.7308	Intermediate Similarity	NPC185639
0.7308	Intermediate Similarity	NPC251735
0.7308	Intermediate Similarity	NPC49075
0.7308	Intermediate Similarity	NPC599951
0.7237	Intermediate Similarity	NPC603853
0.7101	Intermediate Similarity	NPC247639
0.7101	Intermediate Similarity	NPC25084
0.7089	Intermediate Similarity	NPC223690
0.7089	Intermediate Similarity	NPC9532
0.6923	Remote Similarity	NPC480587
0.6914	Remote Similarity	NPC181796
0.6914	Remote Similarity	NPC290005
0.6914	Remote Similarity	NPC54654
0.6914	Remote Similarity	NPC7715
0.6914	Remote Similarity	NPC328155
0.6914	Remote Similarity	NPC222661
0.6914	Remote Similarity	NPC285931
0.6867	Remote Similarity	NPC24260
0.6867	Remote Similarity	NPC611658
0.679	Remote Similarity	NPC229373
0.675	Remote Similarity	NPC286119
0.6747	Remote Similarity	NPC212237
0.6625	Remote Similarity	NPC608819
0.6585	Remote Similarity	NPC274716
0.6585	Remote Similarity	NPC167116
0.6585	Remote Similarity	NPC609821
0.6538	Remote Similarity	NPC227060
0.6316	Remote Similarity	NPC30779
0.625	Remote Similarity	NPC480586
0.625	Remote Similarity	NPC480590
0.6203	Remote Similarity	NPC41376
0.6184	Remote Similarity	NPC317272
0.6184	Remote Similarity	NPC268503
0.6154	Remote Similarity	NPC256012
0.6154	Remote Similarity	NPC610965
0.6076	Remote Similarity	NPC480592
0.6049	Remote Similarity	NPC240841
0.6047	Remote Similarity	NPC16357
0.6047	Remote Similarity	NPC302245
0.6047	Remote Similarity	NPC195538
0.6	Remote Similarity	NPC82457
0.5977	Remote Similarity	NPC243454
0.5972	Remote Similarity	NPC317439
0.5946	Remote Similarity	NPC104196
0.5909	Remote Similarity	NPC8836
0.5909	Remote Similarity	NPC485712
0.5854	Remote Similarity	NPC610959
0.5824	Remote Similarity	NPC11296
0.5824	Remote Similarity	NPC274661
0.5806	Remote Similarity	NPC41122
0.5806	Remote Similarity	NPC318805
0.5795	Remote Similarity	NPC475479
0.5795	Remote Similarity	NPC323537
0.5753	Remote Similarity	NPC135538
0.5753	Remote Similarity	NPC24233
0.573	Remote Similarity	NPC275680
0.573	Remote Similarity	NPC22115
0.5652	Remote Similarity	NPC206900
0.5604	Remote Similarity	NPC10871
0.5604	Remote Similarity	NPC239584
0.5595	Remote Similarity	NPC480591
0.5591	Remote Similarity	NPC485711
0.5581	Remote Similarity	NPC475393
0.5581	Remote Similarity	NPC600872
0.5484	Remote Similarity	NPC281581
0.5444	Remote Similarity	NPC139783
0.5444	Remote Similarity	NPC65312
0.5444	Remote Similarity	NPC601489
0.5444	Remote Similarity	NPC604804
0.5444	Remote Similarity	NPC611798
0.5402	Remote Similarity	NPC600054
0.5402	Remote Similarity	NPC601504
0.5385	Remote Similarity	NPC249996
0.5352	Remote Similarity	NPC213206
0.5352	Remote Similarity	NPC188163
0.5352	Remote Similarity	NPC328750
0.5258	Remote Similarity	NPC48490
0.5211	Remote Similarity	NPC314682
0.5204	Remote Similarity	NPC175890
0.52	Remote Similarity	NPC147390
0.52	Remote Similarity	NPC428
0.5169	Remote Similarity	NPC601503
0.5158	Remote Similarity	NPC254581
0.5155	Remote Similarity	NPC475597
0.5135	Remote Similarity	NPC185838
0.5102	Remote Similarity	NPC60295
0.5098	Remote Similarity	NPC475654
0.5054	Remote Similarity	NPC605743
0.5051	Remote Similarity	NPC201508

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC548600 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4704
0.1-0.2	4341
0.2-0.3	90
0.3-0.4	8
0.4-0.5	1
0.5-0.6	3
0.6-0.7	0
0.7-0.8	3
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
0.7887	Intermediate Similarity	NPD8099	Discontinued
0.7467	Intermediate Similarity	NPD8156	Discontinued
0.7143	Intermediate Similarity	NPD8095	Phase 1
0.5361	Remote Similarity	NPD8054	Phase 4
0.5352	Remote Similarity	NPD4664	Clinical (unspecified phase)
0.5258	Remote Similarity	NPD8053	Approved

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