NPASS Compound

Natural Product: NPC515159

Natural Product ID	NPC515159
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	6-DEOXYDAUNOMYCIN
IUPAC Name	(7~{S},9~{S})-9-acetyl-7-[(2~{R},4~{S},5~{S},6~{S})-4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl]oxy-6,9-dihydroxy-4-methoxy-8,10-dihydro-7~{H}-tetracene-5,12-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 66 70 0 0 0 0 0 0 0 0999 V2000 5.8965 3.3223 -2.6181 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1163 2.3934 -1.8903 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6436 1.5048 -0.9833 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0096 1.4468 -0.7037 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4258 0.5269 0.2139 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5497 -0.3251 0.8548 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2066 -0.2699 0.5816 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7451 0.6503 -0.3437 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3193 0.7101 -0.6348 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9272 1.5623 -1.4857 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3547 -0.1651 0.0133 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8053 -1.0771 0.9294 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8831 -1.9049 1.5402 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5502 -1.8077 1.2302 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5084 -2.6681 1.8304 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3674 -3.2800 0.7449 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.6420 -4.3399 0.2088 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5643 -3.8479 1.4216 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7983 -5.3129 1.4358 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3909 -3.1425 1.9847 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7458 -2.3083 -0.3461 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3920 -0.8730 0.0479 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7096 -0.0501 -0.9837 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7239 0.8493 -0.7271 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.2076 2.2462 -0.8115 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3600 3.2164 -0.8569 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0197 4.3060 0.0717 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.6366 2.6122 -0.3479 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.5830 2.6407 1.0453 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9447 1.2630 -0.8963 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5362 0.3550 0.1761 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8542 0.6390 -1.5054 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0595 -0.8800 0.2941 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0010 -0.0799 -0.2891 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6224 0.8639 -1.2249 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2292 -1.1403 1.2231 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6288 -1.9852 2.0687 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3591 4.0689 -1.9205 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6841 2.8373 -3.2084 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2599 3.9031 -3.3159 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6392 2.1344 -1.2340 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5009 0.4793 0.4357 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9024 -1.0499 1.5819 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2227 -2.6257 2.2614 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0963 -2.1378 2.5961 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0039 -3.5108 2.3577 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3878 -4.9459 0.9385 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2742 -5.8058 2.2907 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4978 -5.7994 0.4897 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8959 -5.5270 1.5445 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1479 -2.5344 -1.2510 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8363 -2.3247 -0.5390 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0020 -0.6152 0.9689 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0503 0.6692 0.3307 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5656 2.4099 0.1021 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5798 2.4425 -1.7034 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5148 3.6589 -1.8464 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6890 5.0961 -0.0834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0880 4.6670 -0.2784 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4597 3.3318 -0.6265 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3465 3.0960 1.4600 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7232 1.3595 -1.6812 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3867 -0.7160 -0.0714 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6319 0.5238 0.2040 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0539 0.5432 1.1565 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6658 0.7209 -2.2271 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 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 6 16 18 1 0 18 19 1 0 18 20 2 0 16 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 26 28 1 0 28 29 1 0 28 30 1 0 30 31 1 0 30 32 1 0 22 33 1 0 33 34 2 0 34 35 1 0 12 36 1 0 36 37 2 0 8 3 1 0 34 11 1 0 36 7 1 0 33 14 1 0 32 24 1 0 1 38 1 0 1 39 1 0 1 40 1 0 4 41 1 0 5 42 1 0 6 43 1 0 13 44 1 0 15 45 1 0 15 46 1 0 17 47 1 0 19 48 1 0 19 49 1 0 19 50 1 0 21 51 1 0 21 52 1 0 22 53 1 1 24 54 1 1 25 55 1 0 25 56 1 0 26 57 1 6 27 58 1 0 27 59 1 0 28 60 1 6 29 61 1 0 30 62 1 6 31 63 1 0 31 64 1 0 31 65 1 0 35 66 1 0 M END

Standard InCHIKey	ZCLQMQOBRBUQOR-GRRPPOEGSA-N
Standard InCHI	InChI=1S/C27H29NO9/c1-11-23(30)16(28)8-19(36-11)37-18-10-27(34,12(2)29)9-13-7-15-22(25(32)20(13)18)26(33)21-14(24(15)31)5-4-6-17(21)35-3/h4-7,11,16,18-19,23,30,32,34H,8-10,28H2,1-3H3/t11-,16-,18-,19-,23+,27-/m0/s1
SMILES	COC1=CC=CC2=C1C(=O)C1=C(C=C3C[C@@](O)(C(C)=O)C[C@H](O[C@H]4C[C@H](N)[C@H](O)[C@H](C)O4)C3=C1O)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	511.18	Volume:	499.146 ? Van der Waals volume.
Dense:	1.024	LogP:	1.579 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.042 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.853 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	30.0
TPSA:	165.61 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	5.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.401	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.45	Fsp³:	0.444
MCE-18:	117.692 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	1
Colloidal aggregators:	0.632	Fluc inhibitor:	0.046 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.323 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.939 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.006	Promiscuous compounds:	0.857

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.422	MDCK Permeability:	-5.344
Pgp-inhibitor:	0.02	Pgp-substrate:	0.994
PAMPA:	0.997 ? 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):	0.593
20% Bioavailability (F20%):	0.804	30% Bioavailability (F30%):	0.979
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.981
Plasma Protein Binding (PPB):	93.818%	Volume Distribution (VD):	1.355
Fu:	8.095% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.958
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.07
BSEP inhibitor:	0.093

ADMET: Metabolism

CYP1A2-inhibitor:	0.008	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.971
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.94
HLM stability:	0.076 ? 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):

5.582

Half-life (T1/2):

2.447

ADMET: Toxicity

hERG Blockers:	0.299	hERG Blockers (10um):	0.467
Human Hepatotoxicity (H-HT):	0.989	Drug-induced Liver Injury (DILI):	0.997
AMES Toxicity:	0.99	Rat Oral Acute Toxicity:	0.948
Maximum Recommended Daily Dose:	0.985	Skin Sensitization:	0.999
Carcinogencity:	0.955	Eye Corrosion:	0.0
Eye Irritation:	0.024	Respiratory Toxicity:	0.978
Drug-induced Neurotoxicity:	0.941	Ototoxicity:	0.98
Hematotoxicity:	0.882	Drug-induced Nephrotoxicity:	0.992
Genotoxicity:	0.997	RPMI-8226 Immunitoxicity:	0.777
A549 Cytotoxicity:	0.999	Hek293 Cytotoxicity:	0.93
BCF:	0.939 ? 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:	3.655 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.179 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.571 ? 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
NPO56281	Micromonospora peucetica	Species	Micromonosporaceae	Bacteria	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 NPC515159 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	11861
0.1-0.2	35797
0.2-0.3	2146
0.3-0.4	41
0.4-0.5	4
0.5-0.6	2
0.6-0.7	2
0.7-0.8	6
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
0.8077	Intermediate Similarity	NPC109403
0.7975	Intermediate Similarity	NPC487573
0.7349	Intermediate Similarity	NPC261012
0.7349	Intermediate Similarity	NPC314738
0.7262	Intermediate Similarity	NPC468994
0.7073	Intermediate Similarity	NPC603200
0.6824	Remote Similarity	NPC601855
0.65	Remote Similarity	NPC611971
0.5978	Remote Similarity	NPC600087
0.5281	Remote Similarity	NPC602774

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC515159 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2719
0.1-0.2	6321
0.2-0.3	78
0.3-0.4	5
0.4-0.5	6
0.5-0.6	12
0.6-0.7	2
0.7-0.8	6
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8077	Intermediate Similarity	NPD6778	Phase 4
0.7975	Intermediate Similarity	NPD6777	Approved
0.7349	Intermediate Similarity	NPD6781	Phase 4
0.7349	Intermediate Similarity	NPD6782	Phase 4
0.7262	Intermediate Similarity	NPD6779	Approved
0.7262	Intermediate Similarity	NPD6780	Approved
0.7	Intermediate Similarity	NPD6776	Approved
0.65	Remote Similarity	NPD6535	Phase 4
0.642	Remote Similarity	NPD6534	Approved
0.5755	Remote Similarity	NPD8058	Clinical (unspecified phase)
0.5755	Remote Similarity	NPD8059	Phase 3
0.5579	Remote Similarity	NPD6823	Phase 2
0.54	Remote Similarity	NPD7871	Phase 2
0.5385	Remote Similarity	NPD7801	Approved
0.537	Remote Similarity	NPD8155	Clinical (unspecified phase)
0.5347	Remote Similarity	NPD7696	Phase 3
0.5347	Remote Similarity	NPD7697	Phase 3
0.5347	Remote Similarity	NPD7698	Approved
0.5347	Remote Similarity	NPD7870	Phase 2
0.5104	Remote Similarity	NPD7699	Phase 2
0.5104	Remote Similarity	NPD7700	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